Scholars@Duke
Piotr E. Marszalek

Piotr E. Marszalek

Professor in the Thomas Lord Department of Mechanical Engineering and Materials Science
Thomas Lord Department of Mechanical Engineering and Materials Science
pemar@duke.edu
3387 FCIEMAS Building, Box 90300, Durham, NC 27708-0300
3387 FCIEMAS Building, Box 90300, Durham, NC 27708

Selected Publications

Nanoluc oligoproteins as a model system for protein misfolding and refolding studies.

Journal Article Biophysical journal · December 2025 Protein misfolding can lead to protein malfunction, which may compromise cell viability. Chaperones, including the HSP70 system, are proteins that have evolved to restore the native structure of misfolded proteins. Although most chaperones, including DnaK ... Full text Cite

Denaturation of firefly luciferase at heat shock temperatures captured in silico.

Journal Article Biophysical journal · August 2025 Firefly luciferase (Fluc) is a bioluminescent protein that is widely used in cell and molecular biology research. Specifically, it is a gold standard substrate in chaperone protein studies because its bioluminescence decrease and recovery are related to Fl ... Full text Cite

Tandem repeats of highly bioluminescent NanoLuc are refolded noncanonically by the Hsp70 machinery.

Journal Article Protein science : a publication of the Protein Society · February 2024 Chaperones are a large family of proteins crucial for maintaining cellular protein homeostasis. One such chaperone is the 70 kDa heat shock protein (Hsp70), which plays a crucial role in protein (re)folding, stability, functionality, and translocation. Whi ... Full text Cite

Ligand-Mediated Mechanical Enhancement in Protein Complexes at Nano- and Macro-Scale.

Journal Article ACS applied materials & interfaces · January 2024 Protein self-assembly plays a vital role in a myriad of biological functions and in the construction of biomaterials. Although the physical association underlying these assemblies offers high specificity, the advantage often compromises the overall durabil ... Full text Cite

Special Issue: 18th Congress of the Polish Biophysical Society.

Journal Article European biophysics journal : EBJ · October 2023 The 18th Congress of the Polish Biophysical Society took place at the Faculty of Physics of the University of Warsaw in Warsaw, Poland, in September 2022. In total, 111 attendees (Attendance Profile: 107 in-person, 4 remote; Italy 1, Lithuania 1, Poland 10 ... Full text Cite

Mechanical Unfolding and Refolding of NanoLuc via Single-Molecule Force Spectroscopy and Computer Simulations.

Journal Article Biomacromolecules · December 2022 A highly bioluminescent protein, NanoLuc (Nluc), has seen numerous applications in biological assays since its creation. We recently engineered a NanoLuc polyprotein that showed high bioluminescence but displayed a strong misfolding propensity after mechan ... Full text Cite

Capturing intrinsic nanomechanics of allostery.

Journal Article Biophysical journal · December 2022 The Hsp70 chaperone exploits allosteric communication between its substrate binding domain and its nucleotide binding domain to regulate the loading and release of misfolded polypeptides in an ATP-hydrolysis-dependent manner. In this issue of Biophysical J ... Full text Cite

Reconstruction of mechanical unfolding and refolding pathways of proteins with atomic force spectroscopy and computer simulations.

Journal Article Methods (San Diego, Calif.) · January 2022 Most proteins in proteomes are large, typically consist of more than one domain and are structurally complex. This often makes studying their mechanical unfolding pathways challenging. Proteins composed of tandem repeat domains are a subgroup of multi-doma ... Full text Cite

Piecewise All-Atom SMD Simulations Reveal Key Secondary Structures in Luciferase Unfolding Pathway.

Journal Article Biophysical journal · December 2020 Although the folding of single-domain proteins is well characterized theoretically and experimentally, the folding of large multidomain proteins is less well known. Firefly luciferase, a 550 residue three-domain protein, has been commonly used as a substra ... Full text Cite

Mechanical Stability of a Small, Highly-Luminescent Engineered Protein NanoLuc.

Journal Article International journal of molecular sciences · December 2020 NanoLuc is a bioluminescent protein recently engineered for applications in molecular imaging and cellular reporter assays. Compared to other bioluminescent proteins used for these applications, like Firefly Luciferase and Renilla Luciferase, it is ~150 ti ... Full text Cite

Meeting report - NSF-sponsored workshop 'Progress and Prospects of Single-Molecule Force Spectroscopy in Biological and Chemical Sciences'.

Journal Article Journal of cell science · August 2020 The goals of the workshop organized by Piotr Marszalek and Andres Oberhauser that took place between 29 August and 1 September 2019 at Duke University were to bring together leading experts and junior researchers to review past accomplishments, recent adva ... Full text Cite

Exploiting a Mechanical Perturbation of a Titin Domain to Identify How Force Field Parameterization Affects Protein Refolding Pathways.

Journal Article Journal of chemical theory and computation · May 2020 Molecular mechanics force fields have been shown to differ in their predictions of biomolecular processes such as protein folding. To test how force field differences affect predicted polypeptide behavior, we created a mechanically perturbed model of the β ... Full text Cite

An estimate to the first approximation of microtubule rupture force.

Journal Article Eur Biophys J · September 2019 Microtubule mechanical properties are essential for understanding basic cellular processes, including cell motility and division, but the forces that result in microtubule rupture or breakage have not yet been measured directly. These forces are essential ... Full text Link to item Cite

Force Spectroscopy of Single Protein Molecules Using an Atomic Force Microscope.

Journal Article Journal of visualized experiments : JoVE · February 2019 The determination of the folding process of proteins from their amino acid sequence to their native 3D structure is an important problem in biology. Atomic force microscopy (AFM) can address this problem by enabling stretching and relaxation of single prot ... Full text Cite

Endonuclease-independent DNA mismatch repair processes on the lagging strand.

Journal Article DNA repair · August 2018 DNA mismatch repair (MMR) pathways coordinate the excision and re-synthesis of newly-replicated DNA if a mismatched base-pair has been identified by protein MutS or MutS homologues (MSHs) after replication. DNA excision during MMR is initiated at single-st ... Full text Cite

Unraveling the Mechanical Unfolding Pathways of a Multidomain Protein: Phosphoglycerate Kinase.

Journal Article Biophysical journal · July 2018 Phosphoglycerate kinase (PGK) is a highly conserved enzyme that is crucial for glycolysis. PGK is a monomeric protein composed of two similar domains and has been the focus of many studies for investigating interdomain interactions within the native state ... Full text Cite

Relevance of the Speed and Direction of Pulling in Simple Modular Proteins.

Journal Article Journal of chemical theory and computation · June 2018 A theoretical framework capable of predicting the first unit that unfolds in pulled modular proteins has been recently introduced, for "fast enough" pulling velocities. Within this picture, we investigate the unfolding pathway in a chain of identical units ... Full text Cite

Spermidine-Induced Attraction of Like-Charged Surfaces Is Correlated with the pH-Dependent Spermidine Charge: Force Spectroscopy Characterization.

Journal Article Langmuir : the ACS journal of surfaces and colloids · February 2018 The ubiquitous molecule spermidine is known for its pivotal roles in the contact mediation, fusion, and reorganization of biological membranes and DNA. In our model system, borosilicate beads were attached to atomic force microscopy cantilevers and used to ... Full text Cite

Warhammers for Peaceful Times.

Journal Article Biophysical journal · January 2018 The Perkins group has recently developed a number of improved atomic force microscopy cantilevers using the focused ion beam technology. They compared the performance of these cantilevers in "real-life" biophysical single-molecule force spectroscopy measur ... Full text Cite

AFM-Based Single-Molecule Force Spectroscopy of Proteins.

Journal Article Methods in molecular biology (Clifton, N.J.) · January 2018 Single-molecule force spectroscopy by AFM (AFM-SMFS) is an experimental methodology that allows unequivocal sensitivity and control for investigating and manipulating the mechanical properties of single molecules. The past 20 years of AFM-SMFS has provided ... Full text Cite

A 'Semi-Protected Oligonucleotide Recombination' Assay for DNA Mismatch Repair in vivo Suggests Different Modes of Repair for Lagging Strand Mismatches.

Journal Article Nucleic acids research · May 2017 In Escherichia coli, a DNA mismatch repair (MMR) pathway corrects errors that occur during DNA replication by coordinating the excision and re-synthesis of a long tract of the newly-replicated DNA between an epigenetic signal (a hemi-methylated d(GATC) sit ... Full text Cite

Competing Pathways and Multiple Folding Nuclei in a Large Multidomain Protein, Luciferase.

Journal Article Biophysical journal · May 2017 Proteins obtain their final functional configuration through incremental folding with many intermediate steps in the folding pathway. If known, these intermediate steps could be valuable new targets for designing therapeutics and the sequence of events cou ... Full text Cite

Strong, Tough, Stretchable, and Self-Adhesive Hydrogels from Intrinsically Unstructured Proteins

Journal Article Advanced Materials · 2017 An experiment has demonstrated that genetically engineered unstructured proteins with covalent and reversible crosslinking (due to metal coordination and hydrophobic interactions) yield hydrogels with extremely high strength, toughness, stretchability, and ... Full text Cite

Atomic force microscope force spectroscopy

Chapter · January 1, 2017 The ability to pull on or stretch individual molecules with subnanometer-scale precision provides a way to directly investigate the underlying physical properties of the biological molecules involved in life’s processes. This ability is realized when perfo ... Full text Cite

Can Dissipative Properties of Single Molecules Be Extracted from a Force Spectroscopy Experiment?

Journal Article Biophysical journal · September 2016 We performed dynamic force spectroscopy of single dextran and titin I27 molecules using small-amplitude and low-frequency (40-240 Hz) dithering of an atomic force microscope tip excited by a sine wave voltage fed onto the tip-carrying piezo. We show that f ... Full text Cite

Single-molecule Force Spectroscopy Reveals the Calcium Dependence of the Alternative Conformations in the Native State of a βγ-Crystallin Protein.

Journal Article The Journal of biological chemistry · August 2016 Although multidomain proteins predominate the proteome of all organisms and are expected to display complex folding behaviors and significantly greater structural dynamics as compared with single-domain proteins, their conformational heterogeneity and its ... Full text Cite

Influence of the frequency stability on the emitter position in SDF method

Conference 2016 International Conference on Military Communications and Information Systems Icmcis 2016 · June 20, 2016 An accuracy of each location method depends primarily on an accuracy of a parameter measurements that is the basis of the method. In the case of frequency methods, a frequency stability of a localized emitter is the main factor influencing on the location ... Full text Cite

Atomic force microscopy captures the initiation of methyl-directed DNA mismatch repair.

Journal Article DNA repair · November 2015 In Escherichia coli, errors in newly-replicated DNA, such as the incorporation of a nucleotide with a mis-paired base or an accidental insertion or deletion of nucleotides, are corrected by a methyl-directed mismatch repair (MMR) pathway. While the enzymol ... Full text Cite

Structure and specificity of the RNA-guided endonuclease Cas9 during DNA interrogation, target binding and cleavage.

Journal Article Nucleic acids research · October 2015 CRISPR-associated endonuclease Cas9 cuts DNA at variable target sites designated by a Cas9-bound RNA molecule. Cas9's ability to be directed by single 'guide RNA' molecules to target nearly any sequence has been recently exploited for a number of emerging ... Full text Cite

Direct observation of multimer stabilization in the mechanical unfolding pathway of a protein undergoing oligomerization.

Journal Article ACS nano · February 2015 Understanding how protein oligomerization affects the stability of monomers in self-assembled structures is crucial to the development of new protein-based nanomaterials and protein cages for drug delivery. Here, we use single-molecule force spectroscopy ( ... Full text Cite

Intramolecular immunological signal hypothesis revived--structural background of signalling revealed by using Congo Red as a specific tool.

Journal Article Mini reviews in medicinal chemistry · January 2015 Micellar structures formed by self-assembling Congo red molecules bind to proteins penetrating into function-related unstable packing areas. Here, we have used Congo red--a supramolecular protein ligand--to investigate how the intramolecular structural cha ... Full text Cite

Capturing the mechanical unfolding pathway of a large protein with coiled-coil probes.

Journal Article Angewandte Chemie (International ed. in English) · December 2014 The folding behaviors and mechanisms of large multidomain proteins have remained largely uncharacterized, primarily because of the lack of appropriate research methods. To address these limitations, novel mechanical folding probes have been developed that ... Full text Cite

Cognitive manager for hierarchical cluster networks based on multi-stage machine method

Conference Proceedings IEEE Military Communications Conference MILCOM · November 13, 2014 Apart from efficient use of assigned spectral resources as a primary user, Cognitive Radio (CR) has the ability to act as a secondary user, utilizing available radio resources, which are not used by primary users for a certain period of time. This paper re ... Full text Cite

Chaperones rescue luciferase folding by separating its domains.

Journal Article The Journal of biological chemistry · October 2014 Over the last 50 years, significant progress has been made toward understanding how small single-domain proteins fold. However, very little is known about folding mechanisms of medium and large multidomain proteins that predominate the proteomes of all for ... Full text Cite

Single molecule mechanical manipulation for studying biological properties of proteins, DNA, and sugars.

Journal Article Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology · May 2014 For over 20 years there has been immense biological insight gained using single molecule mechanical measurements to understand properties of biomolecules. This review outlines the field of single molecule mechanics studies and focuses on the manipulation o ... Full text Cite

Improving single molecule force spectroscopy through automated real-time data collection and quantification of experimental conditions.

Journal Article Ultramicroscopy · January 2014 The benefits of single molecule force spectroscopy (SMFS) clearly outweigh the challenges which include small sample sizes, tedious data collection and introduction of human bias during the subjective data selection. These difficulties can be partially eli ... Full text Cite

Origin of overstretching transitions in single-stranded nucleic acids.

Journal Article Physical review letters · November 2013 We combined single-molecule force spectroscopy with nuclear magnetic resonance measurements and molecular mechanics simulations to examine overstretching transitions in single-stranded nucleic acids. In single-stranded DNA and single-stranded RNA there is ... Full text Cite

Origin of overstretching transitions in single-stranded nucleic acids

Journal Article Physical review letters · November 1, 2013 We combined single-molecule force spectroscopy with nuclear magnetic resonance measurements and molecular mechanics simulations to examine overstretching transitions in single-stranded nucleic acids. In single-stranded DNA and single-stranded RNA there is ... Cite

A single-molecule stretching method for lateral and normal AFM lever calibration.

Journal Article Nanotechnology · September 2013 A novel method for quantitative lateral force measurement (LFM) calibration has been developed. Using a single-molecule spectroscopy approach it is possible to calibrate the AFM levers for both lateral and normal spring constants with a single image scan. ... Full text Cite

Effects of ligand binding on the mechanical properties of ankyrin repeat protein gankyrin.

Journal Article PLoS computational biology · January 2013 Ankyrin repeat proteins are elastic materials that unfold and refold sequentially, repeat by repeat, under force. Herein we use atomistic molecular dynamics to compare the mechanical properties of the 7-ankyrin-repeat oncoprotein Gankyrin in isolation and ... Full text Cite

Atomic force microscopy captures folded ribosome bound nascent chains.

Journal Article Chemical communications (Cambridge, England) · December 2012 Direct visualization of co-translational folding of nascent polypeptide chains is challenging. Here we present, for the first time, AFM images of large protein constructs based on the membrane binding domain of ankyrin-R, complexed with the ribosome. The c ... Full text Cite

Mutation of conserved histidines alters tertiary structure and nanomechanics of consensus ankyrin repeats.

Journal Article J Biol Chem · June 1, 2012 The conserved TPLH tetrapeptide motif of ankyrin repeats (ARs) plays an important role in stabilizing AR proteins, and histidine (TPLH)-to-arginine (TPLR) mutations in this motif have been associated with a hereditary human anemia, spherocytosis. Here, we ... Full text Link to item Cite

Stretching single polysaccharides and proteins using atomic force microscopy.

Journal Article Chemical Society reviews · May 2012 The past years have witnessed remarkable advances in our use of atomic force microscopy (AFM) for stretching single biomolecules, thereby contributing to answering many outstanding questions in biophysics and chemical biology. In these single-molecule forc ... Full text Cite

Triple stimulus-responsive polypeptide nanoparticles that enhance intratumoral spatial distribution.

Journal Article Nano letters · April 2012 To address the limited tumor penetration of nanoparticle drug delivery vehicles, we report the first pH-responsive polypeptide micelle that dissociates at the low extracellular pH of solid tumors. This histidine-rich elastin-like polypeptide block copolyme ... Full text Cite

Mechanical anisotropy of ankyrin repeats.

Journal Article Biophys J · March 7, 2012 Red blood cells are frequently deformed and their cytoskeletal proteins such as spectrin and ankyrin-R are repeatedly subjected to mechanical forces. While the mechanics of spectrin was thoroughly investigated in vitro and in vivo, little is known about th ... Full text Link to item Cite

A nanoscale force probe for gauging intermolecular interactions.

Journal Article Angewandte Chemie (International ed. in English) · February 2012 Full text Cite

Nanomechanics of streptavidin hubs for molecular materials.

Journal Article Adv Mater · December 15, 2011 A new strategy is reported for creating protein-based nanomaterials by genetically fusing large polypeptides to monomeric streptavidin and exploiting the propensity of streptavidin monomers(SM) to self-assemble into stable tetramers. We have characterized ... Full text Link to item Cite

Atomic force microscopy captures MutS tetramers initiating DNA mismatch repair.

Journal Article The EMBO journal · June 2011 In spite of extensive research, the mechanism by which MutS initiates DNA mismatch repair (MMR) remains controversial. We use atomic force microscopy (AFM) to capture how MutS orchestrates the first step of E. coli MMR. AFM images captured two types of Mut ... Full text Cite

Inhibitor binding increases the mechanical stability of staphylococcal nuclease.

Journal Article Biophysical journal · February 2011 Staphylococcal nuclease (SNase) catalyzes the hydrolysis of DNA and RNA in a calcium-dependent fashion. We used AFM-based single-molecule force spectroscopy to investigate the mechanical stability of SNase alone and in its complex with an SNase inhibitor, ... Full text Cite

Mechanics of polysaccharides

Chapter · January 1, 2011 Cite

Full reconstruction of a vectorial protein folding pathway by atomic force microscopy and molecular dynamics simulations.

Journal Article J Biol Chem · December 3, 2010 During co-translational folding, the nascent polypeptide chain is extruded sequentially from the ribosome exit tunnel and is [corrected] under severe conformational constraints [corrected] dictated by the one-dimensional geometry of the tunnel. [corrected] ... Full text Link to item Cite

DNA sequencing: detecting methylation with force.

Journal Article Nature nanotechnology · November 2010 Full text Cite

Separating DNA with different topologies by atomic force microscopy in comparison with gel electrophoresis.

Journal Article The journal of physical chemistry. B · September 2010 Atomic force microscopy, which is normally used for DNA imaging to gain qualitative results, can also be used for quantitative DNA research, at a single-molecular level. Here, we evaluate the performance of AFM imaging specifically for quantifying supercoi ... Full text Open Access Cite

Fast and forceful refolding of stretched alpha-helical solenoid proteins.

Journal Article Biophys J · June 16, 2010 Anfinsen's thermodynamic hypothesis implies that proteins can encode for stretching through reversible loss of structure. However, large in vitro extensions of proteins that occur through a progressive unfolding of their domains typically dissipate a signi ... Full text Link to item Cite

Mechanical unfolding of an ankyrin repeat protein.

Journal Article Biophysical journal · April 2010 Ankryin repeat proteins comprise tandem arrays of a 33-residue, predominantly alpha-helical motif that stacks roughly linearly to produce elongated and superhelical structures. They function as scaffolds mediating a diverse range of protein-protein interac ... Full text Cite

Equilibrium sampling for biomolecules under mechanical tension.

Journal Article Biophysical journal · February 2010 In the studies of force-induced conformational transitions of biomolecules, the large timescale difference from experiments presents the challenge of obtaining convergent sampling for molecular dynamics simulations. To circumvent this fundamental problem, ... Full text Cite

A non-invasive assessment of intracranial volume reserve by measuring cerebrospinal fluid volume with the aid of CT imaging.

Journal Article Acta neurochirurgica. Supplement · January 2010 IntroductionMonitoring changes in the intracranial volume (ICV) reserve and intracranial pressure (ICP) is one of the key issues in the treatment of intracranial pathologies. The aim of this study is to develop a method of monitoring the ICV reser ... Full text Cite

Nanomechanical fingerprints of gamma radiation damage to DNA.

Journal Article Journal of nanoscience and nanotechnology · December 2009 The exposure of cancer cells to ionizing radiation results in potentially lethal DNA lesions. For this reason, identification and quantification of various lesions have intensively been investigated. It has also been anticipated that DNA lesions may affect ... Full text Cite

Aligning molecular attachment sites in single molecule force spectroscopy measurements

Journal Article 2008 Proceedings of the ASME International Design Engineering Technical Conferences and Computers and Information in Engineering Conference Detc 2008 · November 23, 2009 In atomic force microscopy (AFM)-based single molecule force spectroscopy, it is assumed that the pulling angle is negligible and that the force applied to the molecule is equivalent to the force measured by the instrument. Although this assumption may hol ... Cite

Mechanically interlocked calix[4]arene dimers display reversible bond breakage under force.

Journal Article Nature nanotechnology · April 2009 The physics of nanoscopic systems is strongly governed by thermal fluctuations that produce significant deviations from the behaviour of large ensembles. Stretching experiments of single molecules offer a unique way to study fundamental theories of statist ... Full text Cite

Detecting solvent-driven transitions of poly(A) to double-stranded conformations by atomic force microscopy.

Journal Article Biophysical journal · April 2009 We report the results of direct measurements by atomic force microscopy of solvent-driven structural transitions within polyadenylic acid (poly(A)). Both atomic force microscopy imaging and pulling measurements reveal complex strand arrangements within pol ... Full text Cite

UVA generates pyrimidine dimers in DNA directly.

Journal Article Biophysical journal · February 2009 There is increasing evidence that UVA radiation, which makes up approximately 95% of the solar UV light reaching the Earth's surface and is also commonly used for cosmetic purposes, is genotoxic. However, in contrast to UVC and UVB, the mechanisms by which ... Full text Cite

Aligning molecular attachment sites in single molecule force spectroscopy measurements

Journal Article Proceedings of the ASME Design Engineering Technical Conference · December 1, 2008 In atomic force microscopy (AFM) -based single molecule force spectroscopy, it is assumed that the pulling angle is negligible and that the force applied to the molecule is equivalent to the force measured by the instrument. Although this assumption may ho ... Full text Cite

Minimizing pulling geometry errors in atomic force microscope single molecule force spectroscopy.

Journal Article Biophysical journal · October 2008 In atomic force microscopy-based single molecule force spectroscopy (AFM-SMFS), it is assumed that the pulling angle is negligible and that the force applied to the molecule is equivalent to the force measured by the instrument. Recent studies, however, ha ... Full text Cite

A method to correct pulling geometry induced errors in single molecule force spectroscopy measurements

Journal Article 2007 Proceedings of the ASME International Design Engineering Technical Conferences and Computers and Information in Engineering Conference Detc2007 · June 13, 2008 In AFM-based single molecule force spectroscopy, it is assumed that the pulling angle is negligible and that the force applied to the molecule is equivalent to the force measured by the instrument. Although this assumption may hold for flexible, compact mo ... Full text Cite

Nanoscale detection of ionizing radiation damage to DNA by atomic force microscopy.

Journal Article Small (Weinheim an der Bergstrasse, Germany) · February 2008 The detection and quantification of ionizing radiation damage to DNA at a single-molecule level by atomic force microscopy (AFM) is reported. The DNA damage-detection technique combining supercoiled plasmid relaxation assay with AFM imaging is a direct and ... Full text Cite

Detecting ultraviolet damage in single DNA molecules by atomic force microscopy.

Journal Article Biophysical journal · September 2007 We report detection and quantification of ultraviolet (UV) damage in DNA at a single molecule level by atomic force microscopy (AFM). By combining the supercoiled plasmid relaxation assay with AFM imaging, we find that high doses of medium wave ultraviolet ... Full text Cite

Direct measurements of base stacking interactions in DNA by single-molecule atomic-force spectroscopy.

Journal Article Physical review letters · July 2007 We investigate the elasticity of two types of single-stranded synthetic DNA homopolydeoxynucletides, poly(dA) and poly(dT), by AFM-based single-molecule force spectroscopy. We find that poly(dT) exhibits the expected entropic elasticity behavior, while pol ... Full text Cite

Nanomechanical fingerprints of UV damage to DNA.

Journal Article Small (Weinheim an der Bergstrasse, Germany) · May 2007 Full text Cite

Pulling geometry-induced errors in single molecule force spectroscopy measurements.

Journal Article Biophysical journal · May 2007 In AFM-based single molecule force spectroscopy, it is tacitly assumed that the pulling direction coincides with the end-to-end vector of the molecule fragment being stretched. By systematically varying the position of the attachment point on the substrate ... Full text Cite

A stochastic, cantilever approach to the evaluation of solution phase thermodynamic quantities.

Journal Article Proceedings of the National Academy of Sciences of the United States of America · February 2007 A cantilever device based on competitive binding of an immobilized receptor to immobilized and soluble ligand and capable of measuring solution-phase thermodynamic quantities is described. Through multiple binary queries, the device stochastically measures ... Full text Cite

Simulating force-induced conformational transitions in polysaccharides with the SMD replica exchange method.

Journal Article Biophysical journal · September 2006 Conventional steered molecular dynamics (SMD) simulations do not readily reproduce equilibrium conditions of atomic force microscopy (AFM) stretch and release measurements of polysaccharides undergoing force-induced conformational transitions because of th ... Full text Cite

Direct detection of the formation of V-amylose helix by single molecule force spectroscopy.

Journal Article Journal of the American Chemical Society · July 2006 An important polysaccharide, amylose crystallizes as a regular single left-handed helix from a propanol, butanol, or iodine solution. However, its solution structure remains elusive because amylose does not form molecular solutions in these solvents, and s ... Full text Cite

Identification of sugar isomers by single-molecule force spectroscopy.

Journal Article Journal of the American Chemical Society · May 2006 The nanomechanical properties of beta-galactan, a 1 --> 4 linked beta-d-galactose polysaccharide, were investigated with AFM-based single-molecule force spectroscopy. AFM captured a unique plateau at 640 pN in the force spectrogram of beta-galactan, which ... Full text Cite

Nanospring behaviour of ankyrin repeats.

Journal Article Nature · March 9, 2006 Ankyrin repeats are an amino-acid motif believed to function in protein recognition; they are present in tandem copies in diverse proteins in nearly all phyla. Ankyrin repeats contain antiparallel alpha-helices that can stack to form a superhelical spiral. ... Full text Link to item Cite

Solvent effects on the elasticity of polysaccharide molecules in disordered and ordered states by single-molecule force spectroscopy

Journal Article Polymer · 2006 Single-molecule force spectroscopy, especially as implemented on an atomic force microscopy (AFM) platform is unique in its ability to apply small (F 1000 pN) stretching forces to individual polymer chains and in this way examines their elasticity and als ... Cite

Mechanical unfolding of ubiquitin molecules.

Journal Article The Journal of chemical physics · November 15, 2005 Mechanical stretching of ubiquitin and of its several repeats are studied through molecular-dynamics simulations. A Go-type model [H. Abe and N. Go, Biopolymers 20, 1013 (1981)] with a realistic contact map and with Lennard-Jones contact interactions is us ... Cite

Mechanical unfolding of ubiquitin molecules.

Journal Article The Journal of chemical physics · November 2005 Mechanical stretching of ubiquitin and of its several repeats are studied through molecular-dynamics simulations. A Go-type model [H. Abe and N. Go, Biopolymers 20, 1013 (1981)] with a realistic contact map and with Lennard-Jones contact interactions is us ... Full text Cite

Zipper-like properties of [poly(L-lysine)+ poly(L-glutamic acid)]beta-pleated molecular self-assembly.

Journal Article Chemical communications (Cambridge, England) · November 2005 Through the application of Molecular Force Spectroscopy, here we demonstrate nanomechanical properties of a beta-pleated, reversible, and pH-controllable molecular "zipper" formed by the spontaneous self-assembly of two sequenceless polypeptides. ... Full text Cite

Direct detection of inter-residue hydrogen bonds in polysaccharides by single-molecule force spectroscopy.

Journal Article Angewandte Chemie (International ed. in English) · April 2005 Full text Cite

Atomic cranks and levers control sugar ring conformations

Journal Article Journal of Physics-Condensed Matter · 2005 In this paper we review the conformational analysis of sugar rings placed under tension during mechanical manipulations of single polysaccharide molecules with the atomic force microscope and during steered molecular dynamics simulations. We examine the ro ... Cite

Detection of inter-residue hydrogen bonds in polysaccharides by AFM

Journal Article Abstracts of Papers of the American Chemical Society · 2005 Cite

UV radiation affects the mechanics of the double helix

Journal Article BIOPHYSICAL JOURNAL · January 1, 2005 Link to item Cite

Transcranial Doppler (TCD) ultrasonography in patients with ventriculomegaly: Investigation of additional parameters for qualifying shunt implantation

Journal Article Polish Journal of Radiology · January 1, 2005 Background: Ventriculomegaly without increased intracranial pressure is observed both in normal-pressure hydrocephalus (NPH) and idiopathic cerebral atrophy (CA). Investigating additional parameters to differentiate these diseases is important for a good q ... Cite

Molecular dynamics simulations of forced conformational transitions in 1,6-linked polysaccharides.

Journal Article Biophysical journal · September 2004 Recent atomic force microscopy stretching measurements of single polysaccharide molecules suggest that their elasticity is governed by force-induced conformational transitions of the pyranose ring. However, the mechanism of these transitions and the mechan ... Full text Cite

Amylose elasticity depends on the solvent dielectric constant.

Journal Article ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY · August 22, 2004 Link to item Cite

Elastic properties of single amylose chains in water: a quantum mechanical and AFM study.

Journal Article Journal of the American Chemical Society · July 2004 Recent single-molecule atomic force microscopy (AFM) experiments have revealed that some polysaccharides display large deviations from force-extension relationships of other polymers which typically behave as simple entropic springs. However, the mechanism ... Full text Cite

Nanomechanical control of glucopyranose rotamers.

Journal Article Journal of the American Chemical Society · May 2004 Single molecules of beta-1 --> 6-linked d-glucose polysaccharides, when stretched in an atomic force microscope, display a hookean-like elasticity unusual for polymers. High-level ab initio calculations and microsecond-scale molecular dynamics simulations ... Full text Cite

Surface-to-surface bridges formed by reversibly assembled polymers.

Journal Article Journal of the American Chemical Society · March 2004 Self-assembled polymers whose main chains are defined by reversible DNA base pairing form bridges between the tip of an atomic force microscope and substrate. The forces associated with the rupture of these assemblies are independent of polymer bridge leng ... Full text Cite

Mechanics of 1,6 linked polysaccharides by AFM and SMD calculations

Journal Article BIOPHYSICAL JOURNAL · January 1, 2004 Link to item Cite

Force-induced conformational transitions in 1,6-linked polysaccharides

Journal Article Abstracts of Papers of the American Chemical Society · 2004 Cite

The force-driven conformations of heparin studied with single molecule force microscopy.

Journal Article Biophysical journal · October 2003 Using single molecule force spectroscopy we examine the response of heparin chains to mechanical stretching. We find that at forces below 200 pN heparin behaves as a simple entropic spring. At approximately 200 pN heparin displays a large enthalpic elastic ... Full text Cite

The mechanical stability of ubiquitin is linkage dependent.

Journal Article Nature structural biology · September 2003 Ubiquitin chains are formed through the action of a set of enzymes that covalently link ubiquitin either through peptide bonds or through isopeptide bonds between their C terminus and any of four lysine residues. These naturally occurring polyproteins allo ... Full text Cite

Linkage-dependent stability in polyubiquitin chains

Journal Article BIOPHYSICAL JOURNAL · February 1, 2003 Link to item Cite

Stretching single molecules into novel conformations using the atomic force microscope

Journal Article Abstracts of Papers of the American Chemical Society · 2003 Cite

Reverse engineering of the giant muscle protein titin.

Journal Article Nature · August 2002 Through the study of single molecules it has become possible to explain the function of many of the complex molecular assemblies found in cells. The protein titin provides muscle with its passive elasticity. Each titin molecule extends over half a sarcomer ... Full text Cite

Chair-boat transitions in single polysaccharide molecules observed with force-ramp AFM.

Journal Article Proceedings of the National Academy of Sciences of the United States of America · April 2002 Under a stretching force, the sugar ring of polysaccharide molecules switches from the chair to the boat-like or inverted chair conformation. This conformational change can be observed by stretching single polysaccharide molecules with an atomic force micr ... Full text Cite

Fingerprinting polysaccharides with single-molecule atomic force microscopy (AFM)

Journal Article Abstracts of Papers of the American Chemical Society · 2002 Cite

Stretching single molecules into novel conformations using the atomic force microscope

Journal Article Abstracts of Papers of the American Chemical Society · 2002 Cite

Mechanical control of the pyranose ring conformations by single molecule AFM

Journal Article Abstracts of Papers of the American Chemical Society · 2002 Cite

Fingerprinting polysaccharides with single-molecule atomic force microscopy.

Journal Article Nature biotechnology · March 2001 We report the use of an atomic force microscopy (AFM)-based force spectroscopy technique to identify, at the single-molecule level, the components of mixtures of polysaccharides. Previously, we showed that the elasticity of certain types of polysaccharides ... Full text Cite

Point mutations alter the mechanical stability of immunoglobulin modules.

Journal Article Nature structural biology · December 2000 Immunoglobulin-like modules are common components of proteins that play mechanical roles in cells such as muscle elasticity and cell adhesion. Mutations in these proteins may affect their mechanical stability and thus may compromise their function. Using s ... Full text Cite

Stretching single molecules into novel conformations using the atomic force microscope.

Journal Article Nature structural biology · September 2000 A dense network of interconnected proteins and carbohydrates forms the complex mechanical scaffold of living tissues. The recently developed technique of single molecule force spectroscopy using the atomic force microscope (AFM) has enabled a detailed anal ... Full text Cite

Atomic force microscopy captures quantized plastic deformation in gold nanowires.

Journal Article Proceedings of the National Academy of Sciences of the United States of America · June 2000 Scanning probe microscopy has become a powerful tool to detect structural changes in small clusters of atoms. Herein, we use an atomic force microscope to measure the length of gold nanowire structures during extension and compression cycles. We have found ... Full text Cite

Mechanical design of proteins studied by single-molecule force spectroscopy and protein engineering.

Journal Article Progress in biophysics and molecular biology · January 2000 Mechanical unfolding and refolding may regulate the molecular elasticity of modular proteins with mechanical functions. The development of the atomic force microscopy (AFM) has recently enabled the dynamic measurement of these processes at the single-molec ... Full text Cite

Mechanical unfolding of titin is under kinetic control

Journal Article BIOPHYSICAL JOURNAL · 2000 Cite

Combined treatment of cerebral aneurysms with utilization of clipping and coiling techniques.

Journal Article Neurologia i neurochirurgia polska · January 2000 Cerebral aneurysm clipping is a widely used and accepted treatment option. However, in some patients in severe condition (IV and V WFNS grade), with aneurysms of basilar and vertebral part of the arterial circulation and with high general surgical risk, di ... Cite

Conformational transitions in single protein and polysaccharide molecules studied with AFM techniques

Journal Article Annual International Conference of the IEEE Engineering in Medicine and Biology Proceedings · December 1, 1999 We use single molecule AFM techniques to trigger mechanical unfolding and mechanical unfolding intermediates in the immunoglobulin modules of an engineered polyprotein. Site directed mutagenesis of the immunoglobulin modules results in well defined mechani ... Cite

Force spectroscopy of cell adhesion molecules

Journal Article Annual International Conference of the IEEE Engineering in Medicine and Biology Proceedings · December 1, 1999 Cellular adhesion molecules are placed under force during the highly specific mechanical interactions that occur between proteins of the cell surface and extracellular matrix. In our laboratory we have developed atomic force microscopy (AFM) techniques to ... Cite

Mechanical unfolding intermediates in titin modules.

Journal Article Nature · November 1999 The modular protein titin, which is responsible for the passive elasticity of muscle, is subjected to stretching forces. Previous work on the experimental elongation of single titin molecules has suggested that force causes consecutive unfolding of each do ... Full text Cite

Single protein misfolding events captured by atomic force microscopy.

Journal Article Nature structural biology · November 1999 Using single protein atomic force microscopy (AFM) techniques we demonstrate that after repeated mechanical extension/relaxation cycles, tandem modular proteins can misfold into a structure formed by two neighboring modules. The misfolding is fully reversi ... Full text Cite

The study of protein mechanics with the atomic force microscope.

Journal Article Trends in biochemical sciences · October 1999 The unfolding and folding of single protein molecules can be studied with an atomic force microscope (AFM). Many proteins with mechanical functions contain multiple, individually folded domains with similar structures. Protein engineering techniques have e ... Full text Cite

The micro-mechanics of single molecules studied with atomic force microscopy.

Journal Article The Journal of physiology · October 1999 The atomic force microscope (AFM) in its force-measuring mode is capable of effecting displacements on an angstrom scale (10 A = 1 nm) and measuring forces of a few piconewtons. Recent experiments have applied AFM techniques to study the mechanical propert ... Full text Cite

Atomic force microscopy captures length phenotypes in single proteins.

Journal Article Proceedings of the National Academy of Sciences of the United States of America · September 1999 We use single-protein atomic force microscopy techniques to detect length phenotypes in an Ig module. To gain amino acid resolution, we amplify the mechanical features of a single module by engineering polyproteins composed of up to 12 identical repeats. W ... Full text Cite

Atomic levers control pyranose ring conformations.

Journal Article Proceedings of the National Academy of Sciences of the United States of America · July 1999 Atomic force microscope manipulations of single polysaccharide molecules have recently expanded conformational chemistry to include force-driven transitions between the chair and boat conformers of the pyranose ring structure. We now expand these observati ... Full text Cite

Mechanical and chemical unfolding of a single protein: a comparison.

Journal Article Proceedings of the National Academy of Sciences of the United States of America · March 1999 Is the mechanical unraveling of protein domains by atomic force microscopy (AFM) just a technological feat or a true measurement of their unfolding? By engineering a protein made of tandem repeats of identical Ig modules, we were able to get explicit AFM d ... Full text Cite

Necrosis and apoptosis of tumor cells in embolized meningiomas: histopathology and P53, BCL-2, CD-68 immunohistochemistry.

Journal Article Folia neuropathologica · January 1999 The preoperative embolization of intracranial meningiomas, used in selected patients to reduce tumor vascularity and blood loss during surgery, may produce ischemic changes and/or tumor necrosis. The aim of the present study was to determine the relationsh ... Cite

Polysaccharide elasticity governed by chair-boat transitions of the glucopyranose ring.

Journal Article Nature · December 1998 Many common, biologically important polysaccharides contain pyranose rings made of five carbon atoms and one oxygen atom. They occur in a variety of cellular structures, where they are often subjected to considerable tensile stress. The polysaccharides are ... Full text Cite

The molecular elasticity of the extracellular matrix protein tenascin.

Journal Article Nature · May 14, 1998 Extracellular matrix proteins are thought to provide a rigid mechanical anchor that supports and guides migrating and rolling cells. Here we examine the mechanical properties of the extracellular matrix protein tenascin by using atomic-force-microscopy tec ... Full text Link to item Cite

The glucopyranose ring: An elastic switch disabled by periodate oxidation

Journal Article MOLECULAR BIOLOGY OF THE CELL · 1998 Cite

Kinetics of release of serotonin from isolated secretory granules. I. Amperometric detection of serotonin from electroporated granules.

Journal Article Biophysical journal · September 1997 We developed a method for measuring the efflux of 5-hydroxytryptamine (5-HT, serotonin) from isolated intact granules of the mast cell of the beige mouse. This method combines electroporation of the vesicle membrane with amperometric detection of 5-HT. A s ... Full text Cite

Kinetics of release of serotonin from isolated secretory granules. II. Ion exchange determines the diffusivity of serotonin.

Journal Article Biophysical journal · September 1997 We measured the efflux of 5-hydroxytryptamine (5-HT, serotonin) from an intact secretory granule extracted from the mast cell of the beige mouse. The efflux was measured with amperometry after rupture of the granule membrane was triggered by electroporatio ... Full text Cite

Fluctuation-driven directional flow in biochemical cycle: further study of electric activation of Na,K pumps.

Journal Article Biophysical journal · June 1997 Directional flow of information and energies is characteristic of many types of biochemical reactions, for instance, ion transport, energy coupling during ATP synthesis, and muscle contraction. Can a fluctuating force field, or a noise, induce such a direc ... Full text Cite

[Multi-stage method for the diagnosis of low-pressure hydrocephalus].

Journal Article Neurologia i neurochirurgia polska · May 1997 Multistage method of low-pressure hydrocephalus diagnosis, elaborated in our department, is discussed. The method consists of four stages: I Clinical and neuropsychological examinations, standard computerized tomography. II Somatosensory evoked potentials. ... Cite

Ion-exchange gel regulates neurotransmitter release through the exocytotic fusion pore.

Journal Article Society of General Physiologists series · January 1996 Cite

Pulsed Laser Imaging Demonstrates the Mechanism of Current Rectification at a Hydrogel Interface

Journal Article Langmuir · November 1, 1995 The accumulation or depletion of charge carriers at a p-n junction results in electronic rectification.1 Similarly, we show that accumulation or depletion of ions underlies ionic rectification at a single hydroge.-electrolyte interface. We monit ... Full text Cite

The secretory granule matrix-electrolyte interface: a homologue of the p-n rectifying junction.

Journal Article Biophysical journal · October 1995 When placed at the tip of a glass micropipette electrode the polymeric matrix of the secretory granule behaves like a diode. The measured current was 100-fold greater at negative potentials compared to positive potentials, and up to sixfold greater than th ... Full text Cite

Cell fission and formation of mini cell bodies by high frequency alternating electric field.

Journal Article Biophysical journal · April 1995 We report the use of high frequency alternating electric fields (AC) to induce deformation of sea urchin eggs, leading to budding of membrane vesicles or fission of cells. Several mini cell bodies can be prepared from a single egg by carefully manipulating ... Full text Cite

Recognition and processing of randomly fluctuating electric signals by Na,K-ATPase.

Journal Article Biophysical journal · September 1994 Previous work has shown that Na,K-ATPase of human erythrocytes can extract free energy from sinusoidal electric fields to pump cations up their respective concentration gradients. Because regularly oscillating waveform is not a feature of the transmembrane ... Full text Cite

Bioelectrorheological model of the cell. 5. Electrodestruction of cellular membrane in alternating electric field.

Journal Article Biophysical journal · July 1993 Recently proposed analysis of the extensil stress developed in a cellular membrane subjected to an alternating electric field (Pawłowski, P., and M. Fikus, 1993. Bioelectrorheological model of the cell. 4. Analysis of the extensil deformation of the membra ... Full text Cite

Electroporation in rotating electric fields

Journal Article Bioelectrochemistry and Bioenergetics · January 1, 1992 The entrance of the fluorescence dye, propidium iodide, into murine myeloma cells after poration of the cytoplasmic membrane by application of a rotating electric field for 100 ms was monitored. The dye becomes strongly fluorescent only when bound to cellu ... Full text Cite

Dielectrophoresis and electrorotation of neurospora slime and murine myeloma cells.

Journal Article Biophysical journal · October 1991 Dielectrophoresis and electrorotation are commonly used to measure dielectric properties and membrane electrical parameters of biological cells. We have derived quantitative relationships for several critical points, defined in Fig. A 1, which characterize ... Full text Cite

Determination of electric parameters of cell membranes by a dielectrophoresis method.

Journal Article Biophysical journal · May 1991 Marszalek, P., J. J. Zielinsky, and M. Fikus (1989. Bioelectrochem. Bioenerg. 22:289-298) have described a novel design for measuring the complete dielectrophoretic spectrum of a single cell. From the analysis of the dielectrophoretic spectrum, the membran ... Full text Cite

Schwan equation and transmembrane potential induced by alternating electric field.

Journal Article Biophysical journal · October 1990 The transmembrane potential generated by an alternating electric field (ac) depends strongly on the frequency of the field and can be calculated using the Schwan Equation. We have measured the critical electric breakdown potential, delta psi crit, of the p ... Full text Cite

A new method for the investigation of cellular dielectrophoresis.

Journal Article Zeitschrift fur Naturforschung. C, Journal of biosciences · September 1989 A new method and a new type of measuring-microchamber for the investigation of cellular dielectrophoresis is presented. The method is based on the observation of the trajectory of a single cell in gravitational and electric fields being crossed and orienta ... Full text Cite

Experimental verification of a theoretical treatment of the mechanism of dielectrophoresis

Journal Article Bioelectrochemistry and Bioenergetics · January 1, 1989 Experimental verification of dielectrophoresis models, proposed 20 years ago by Sher and 6 years ago by Sauer, was carried out by a new method allowing the total dielectrophoretic spectrum of a single cell to be obtained. Measurements of the force acting o ... Full text Cite

Experimental verification of a theoretical treatment of the mechanism of dielectrophoresis

Journal Article Journal of Electroanalytical Chemistry · January 1, 1989 Experimental verification of dielectrophoresis models, proposed 20 years ago by Sher and 6 years ago by Sauer, was carried out by a new method allowing the total dielectrophoresis spectrum of a single cell to be obtained. Measurements of the force acting o ... Full text Cite

The Monte Carlo simulation of pearl chain formation.

Journal Article Radiation and environmental biophysics · January 1987 The phenomenon of pearl chain formation (PCF) is investigated by means of a statistical model using the Monte Carlo method. Fifteen particles (cells) interacting with simple dipole-dipole potential are shown to form chains under the influence of an externa ... Full text Cite

Electrofusion of Neurospora crassa slime cells

Journal Article FEMS Microbiology Letters · January 1, 1985 Optimal conditions were established for cell growth, dielectrophoresis and electrofusion of Neurospora crassa slime mutants. It was concluded that these methods could be applied to genetic manipulations (i.e. transformation and construction of diploid slim ... Full text Cite

Electrofusion of Neurospora crassa slime cells

Journal Article FEMS Microbiology Letters · January 1, 1985 Optimal conditions were established for cell growth, dielectrophoresis and electrofusion of Neurospora crassa slime mutants. It was concluded that these methods could be applied to genetic manipulations (i.e. transformation and construction of diploid slim ... Full text Cite