Scholars@Duke
Brenton D. Hoffman

Brenton D. Hoffman

James L. and Elizabeth M. Vincent Associate Professor of Biomedical Engineering
Biomedical Engineering

Selected Publications

Multimodal segmentation of dynamic subcellular features using quantitative phase imaging and FRET-based sensors [Invited]

Journal Article Journal of the Optical Society of America A: Optics and Image Science, and Vision · November 1, 2024 Understanding cellular responses to mechanical environmental stimuli is important for cellular mechanotransduction studies. While fluorescence microscopy has been used for aiding mechanotransduction research due to its molecular sensitivity, the ability of ... Full text Cite

Detection of fluorescent protein mechanical switching in cellulo.

Journal Article Cell reports methods · July 2024 The ability of cells to sense and respond to mechanical forces is critical in many physiological and pathological processes. However, determining the mechanisms by which forces affect protein function inside cells remains challenging. Motivated by in vitro ... Full text Cite

Coupling during collective cell migration is controlled by a vinculin mechanochemical switch.

Journal Article Proceedings of the National Academy of Sciences of the United States of America · December 2023 The ability of cells to move in a mechanically coupled, coordinated manner, referred to as collective cell migration, is central to many developmental, physiological, and pathophysiological processes. Limited understanding of how mechanical forces and bioc ... Full text Cite

Molecular basis and cellular functions of vinculin-actin directional catch bonding.

Journal Article Nature communications · December 2023 The ability of cells and tissues to respond differentially to mechanical forces applied in distinct directions is mediated by the ability of load-bearing proteins to preferentially maintain physical linkages in certain directions. However, the molecular ba ... Full text Cite

Identifying constitutive and context-specific molecular-tension-sensitive protein recruitment within focal adhesions.

Journal Article Developmental cell · March 2023 Mechanosensitive processes often rely on adhesion structures to strengthen, or mature, in response to applied loads. However, a limited understanding of how the molecular tensions that are experienced by a particular protein affect the recruitment of other ... Full text Cite

A Tale of Two Loads: Modulation of IL-1 Induced Inflammatory Responses of Meniscal Cells in Two Models of Dynamic Physiologic Loading.

Journal Article Front Bioeng Biotechnol · 2022 Meniscus injuries are highly prevalent, and both meniscus injury and subsequent surgery are linked to the development of post-traumatic osteoarthritis (PTOA). Although the pathogenesis of PTOA remains poorly understood, the inflammatory cytokine IL-1 is el ... Full text Link to item Cite

Combined Quantitative Phase Microscopy and Förster Resonance Energy Transfer Imaging for Analyzing Endothelial Cell Shear Stress Response

Conference Optics InfoBase Conference Papers · January 1, 2022 Demonstration of quantitative phase microscopy and Förster resonance energy transfer for analyzing molecular and structural information simultaneously. We focus on signaling pathways and sub-cellular structure for endothelial cells exposed to various flows ... Cite

Simplified Instrument Calibration for Wide-Field Fluorescence Resonance Energy Transfer (FRET) Measured by the Sensitized Emission Method.

Journal Article Cytometry. Part A : the journal of the International Society for Analytical Cytology · April 2021 Fӧrster (or fluorescence) resonance energy transfer (FRET) is a quantifiable energy transfer in which a donor fluorophore nonradiatively transfers its excitation energy to an acceptor fluorophore. A change in FRET efficiency indicates a change of proximity ... Full text Cite

Mechanically induced integrin ligation mediates intracellular calcium signaling with single pulsating cavitation bubbles.

Journal Article Theranostics · January 2021 Therapeutic ultrasound or shockwave has shown its great potential to stimulate neural and muscle tissue, where cavitation microbubble induced Ca2+ signaling is believed to play an important role. However, the pertinent mechanisms are unknown, es ... Full text Cite

Combined quantitative phase microscopy and förster resonance energy transfer for analyzing cell ion dynamics

Conference Optics InfoBase Conference Papers · January 1, 2021 We demonstrate the use of quantitative phase microscopy and Förster resonance energy transfer for analyzing molecular and structural information simultaneously. Specifically, we focus on effects of ion channel modulation on signaling pathways and sub-cellu ... Cite

Comprehensive Endogenous Tagging of Basement Membrane Components Reveals Dynamic Movement within the Matrix Scaffolding.

Journal Article Developmental cell · July 2020 Basement membranes (BMs) are supramolecular matrices built on laminin and type IV collagen networks that provide structural and signaling support to tissues. BM complexity, however, has hindered an understanding of its formation, dynamics, and regulation. ... Full text Cite

FRET efficiency measurement with a low-cost frequency domain fluorescence lifetime imaging microscope

Conference Optics InfoBase Conference Papers · January 1, 2020 We utilize a frequency-domain FLIM system operating at a single modulation frequency in combination with a FRET standards calibration curve to measure the FRET efficiency of the vinculin tension sensor, VinTS, at the focal adhesions of living cells. ... Full text Cite

Molecular Tension Sensors: Moving Beyond Force.

Journal Article Current opinion in biomedical engineering · December 2019 Nearly all cellular processes are sensitive to mechanical inputs, and this plays a major role in diverse physiological processes. Mechanical stimuli are thought to be primarily detected through force-induced changes in protein structure. Approximately a de ... Full text Cite

FRET efficiency measurement in a molecular tension probe with a low-cost frequency-domain fluorescence lifetime imaging microscope.

Journal Article Journal of biomedical optics · December 2019 We demonstrate the possibility of measuring FRET efficiency with a low-cost frequency-domain fluorescence lifetime imaging microscope (FD-FLIM). The system utilizes single-frequency-modulated excitation, which enables the use of cost-effective laser source ... Full text Cite

Extent of Cell Confinement in Microtracks Affects Speed and Results in Differential Matrix Strains.

Journal Article Biophysical journal · November 2019 During metastasis, cancer cells navigate through a spatially heterogeneous extracellular matrix (ECM). Physical properties of ECM, including the degree of confinement, influence cell migration behavior. Here, utilizing in vitro three-dimensional collagen m ... Full text Cite

Altering integrin engagement regulates membrane localization of Kir2.1 channels.

Journal Article Journal of cell science · September 2019 How ion channels localize and distribute on the cell membrane remains incompletely understood. We show that interventions that vary cell adhesion proteins and cell size also affect the membrane current density of inward-rectifier K+ channels (K< ... Full text Cite

TRPV4-mediated calcium signaling in mesenchymal stem cells regulates aligned collagen matrix formation and vinculin tension.

Journal Article Proc Natl Acad Sci U S A · February 5, 2019 Microarchitectural cues drive aligned fibrillar collagen deposition in vivo and in biomaterial scaffolds, but the cell-signaling events that underlie this process are not well understood. Utilizing a multicellular patterning model system that allows for ob ... Full text Link to item Cite

Improving Quality, Reproducibility, and Usability of FRET-Based Tension Sensors.

Journal Article Cytometry. Part A : the journal of the International Society for Analytical Cytology · February 2019 Mechanobiology, the study of how mechanical forces affect cellular behavior, is an emerging field of study that has garnered broad and significant interest. Researchers are currently seeking to better understand how mechanical signals are transmitted, dete ... Full text Cite

Measurement of Force-Sensitive Protein Dynamics in Living Cells Using a Combination of Fluorescent Techniques.

Journal Article Journal of visualized experiments : JoVE · November 2018 Cells sense and respond to physical cues in their environment by converting mechanical stimuli into biochemically-detectable signals in a process called mechanotransduction. A crucial step in mechanotransduction is the transmission of forces between the ex ... Full text Cite

Tunable molecular tension sensors reveal extension-based control of vinculin loading.

Journal Article eLife · July 2018 Molecular tension sensors have contributed to a growing understanding of mechanobiology. However, the limited dynamic range and inability to specify the mechanical sensitivity of these sensors has hindered their widespread use in diverse contexts. Here, we ... Full text Cite

Vinculin Force-Sensitive Dynamics at Focal Adhesions Enable Effective Directed Cell Migration.

Journal Article Biophysical journal · April 2018 Cell migration is a complex process, requiring coordination of many subcellular processes including membrane protrusion, adhesion, and contractility. For efficient cell migration, cells must concurrently control both transmission of large forces through ad ... Full text Cite

Enucleated cells reveal differential roles of the nucleus in cell migration, polarity, and mechanotransduction.

Journal Article The Journal of cell biology · March 2018 The nucleus has long been postulated to play a critical physical role during cell polarization and migration, but that role has not been defined or rigorously tested. Here, we enucleated cells to test the physical necessity of the nucleus during cell polar ... Full text Cite

The "Stressful" Life of Cell Adhesion Molecules: On the Mechanosensitivity of Integrin Adhesome.

Journal Article Journal of biomechanical engineering · February 2018 Cells have evolved into complex sensory machines that communicate with their microenvironment via mechanochemical signaling. Extracellular mechanical cues trigger complex biochemical pathways in the cell, which regulate various cellular processes. Integrin ... Full text Cite

Involvement of a Rac1-Dependent Macropinocytosis Pathway in Plasmid DNA Delivery by Electrotransfection.

Journal Article Mol Ther · March 1, 2017 Electrotransfection is a widely used method for delivering genes into cells with electric pulses. Although different hypotheses have been proposed, the mechanism of electrotransfection remains controversial. Previous studies have indicated that uptake and ... Full text Link to item Cite

Bio-Instructive Cues in Scaffolds for Musculoskeletal Tissue Engineering and Regenerative Medicine

Chapter · January 1, 2017 In vivo, cells are presented with complex and dynamic stimuli from their surrounding microenvironment. These microenvironmental cues direct an array of cell behaviors that are critical to tissue development and regeneration, including differentiation, grow ... Full text Cite

Genetically Encoded Photoactuators and Photosensors for Characterization and Manipulation of Pluripotent Stem Cells.

Journal Article Theranostics · 2017 Our knowledge of pluripotent stem cell biology has advanced considerably in the past four decades, but it has yet to deliver on the great promise of regenerative medicine. The slow progress can be mainly attributed to our incomplete understanding of the co ... Full text Open Access Link to item Cite

Towards a Dynamic Understanding of Cadherin-Based Mechanobiology.

Journal Article Trends in cell biology · December 2015 Cadherin-based cell-cell adhesions are a primary determinant of tissue structure. For several decades, it had been thought that the primary function of these ubiquitous structures was to resist external mechanical loads. Here we review recent evidence that ... Full text Cite

Controlling Cell Geometry Affects the Spatial Distribution of Load Across Vinculin

Journal Article Cellular and Molecular Bioengineering · September 21, 2015 The shape of adherent cells is known to be a key determinant of cellular processes such as proliferation, apoptosis, and differentiation. Manipulation of cell shape affects stem cell differentiation, gene expression, and the response of cells to mechanical ... Full text Cite

Construction, imaging, and analysis of FRET-based tension sensors in living cells.

Journal Article Methods in cell biology · January 2015 Due to an increased appreciation for the importance of mechanical stimuli in many biological contexts, an interest in measuring the forces experienced by specific proteins in living cells has recently emerged. The development and use of Förster resonance e ... Full text Cite

Molecular-Scale Tools for Studying Mechanotransduction.

Journal Article Annual review of biomedical engineering · January 2015 Mechanical stimuli are known to be potent regulators of the form and function of cells and organisms. Although biological regulation has classically been understood in terms of principles from solution biochemistry, advancements in many fields have led to ... Full text Cite

Discovery and characterization of small molecules that target the GTPase Ral.

Journal Article Nature · November 2014 The Ras-like GTPases RalA and RalB are important drivers of tumour growth and metastasis. Chemicals that block Ral function would be valuable as research tools and for cancer therapeutics. Here we used protein structure analysis and virtual screening to id ... Full text Cite

Tension-sensitive actin assembly supports contractility at the epithelial zonula adherens.

Journal Article Current biology : CB · August 2014 BackgroundActomyosin-based contractility acts on cadherin junctions to support tissue integrity and morphogenesis. The actomyosin apparatus of the epithelial zonula adherens (ZA) is built by coordinating junctional actin assembly with Myosin II ac ... Full text Cite

Regulation of Rac1 translocation and activation by membrane domains and their boundaries.

Journal Article Journal of cell science · June 2014 The activation of Rac1 and related Rho GTPases involves dissociation from Rho GDP-dissociation inhibitor proteins and translocation to membranes, where they bind effectors. Previous studies have suggested that the binding of Rac1 to membranes requires, and ... Full text Cite

The role of extracellular matrix elasticity and composition in regulating the nucleus pulposus cell phenotype in the intervertebral disc: a narrative review.

Journal Article Journal of biomechanical engineering · February 2014 Intervertebral disc (IVD) disorders are a major contributor to disability and societal health care costs. Nucleus pulposus (NP) cells of the IVD exhibit changes in both phenotype and morphology with aging-related IVD degeneration that may impact the onset ... Full text Open Access Cite

The detection and role of molecular tension in focal adhesion dynamics.

Journal Article Progress in molecular biology and translational science · January 2014 Cells are exquisitely sensitive to the mechanical nature of their environment, including applied force and the stiffness of the extracellular matrix (ECM). Recent evidence has shown that these variables are critical regulators of diverse processes mediatin ... Full text Cite

The vacuole within: how cellular organization dictates notochord function.

Journal Article Bioarchitecture · 2013 The notochord is an evolutionarily conserved structure that has long been known to play an important role in patterning during embryogenesis. Structurally, the notochord is composed of two cell layers: an outer epithelial-like sheath, and an inner core of ... Full text Link to item Cite

Light-Triggered Myosin Activation for Probing Dynamic Cellular Processes

Journal Article Angewandte Chemie-International Edition · 2011 Cite

Dynamic molecular processes mediate cellular mechanotransduction

Journal Article Nature · 2011 Featured Publication Cellular responses to mechanical forces are crucial in embryonic development and adult physiology, and are involved in numerous diseases, including atherosclerosis, hypertension, osteoporosis, muscular dystrophy, myopathies and cancer. These responses are ... Full text Cite

Development of a fluorescent microsphere technique for rapid histological determination of cerebral blood flow.

Journal Article Brain Res · April 22, 2010 The purpose of this study was to develop a more efficient fluorescent microsphere method to facilitate the rapid use of the histological technique and to enable its use in large tissue regions. Using fluorescent plate/slide imaging technology and automated ... Full text Link to item Cite

Measuring mechanical tension across vinculin reveals regulation of focal adhesion dynamics

Journal Article Nature · 2010 Featured Publication Mechanical forces are central to developmental, physiological and pathological processes1. However, limited understanding of force transmission within sub-cellular structures is a major obstacle to unravelling molecular mechanisms. Here we describe the dev ... Full text Cite

Cell mechanics: dissecting the physical responses of cells to force.

Journal Article Annual review of biomedical engineering · January 2009 It is now widely appreciated that normal tissue morphology and function rely upon cells' ability to sense and generate forces appropriate to their correct tissue context. Although the effects of forces on cells have been studied for decades, our understand ... Full text Cite

Fragility and mechanosensing in a thermalized cytoskeleton model with forced protein unfolding.

Journal Article Physical review. E, Statistical, nonlinear, and soft matter physics · November 2007 We describe a model of cytoskeletal mechanics based on the force-induced conformational change of protein cross-links in a stressed polymer network. Slow deformation of simulated networks containing cross-links that undergo repeated, serial domain unfoldin ... Full text Cite

Multiple-particle tracking and two-point microrheology in cells.

Journal Article Methods in cell biology · January 2007 Mechanical stress and stiffness are increasingly recognized to play important roles in numerous cell biological processes, notably cell differentiation and tissue morphogenesis. Little definite is known, however, about how stress propagates through differe ... Full text Cite

The role of F-actin and myosin in epithelial cell rheology.

Journal Article Biophysical journal · November 2006 Although actin and myosin are important contributors to cell-force generation, shape change, and motility, their contributions to cell stiffness and frequency-dependent rheology have not been conclusively determined. We apply several pharmacological interv ... Full text Cite

Evidence for the role of cell stiffness in modulation of volume-regulated anion channels.

Journal Article Acta physiologica (Oxford, England) · May 2006 AimTo investigate the link between cell stiffness and volume-regulated anion current (VRAC) in aortic endothelium.MethodBovine aortic endothelial cells (BAECs) were exposed to methyl-beta-cyclodextrin (MbetaCD) to deplete cellular cholest ... Full text Cite

Microrheology probes length scale dependent rheology.

Journal Article Physical review letters · March 2006 We exploit the power of microrheology to measure the viscoelasticity of entangled F-actin solutions at different length scales from 1 to 100 microm over a wide frequency range. We compare the behavior of single probe-particle motion to that of the correlat ... Full text Cite

The consensus mechanics of cultured mammalian cells

Journal Article Proceedings of the National Academy of Sciences of the United States of America · 2006 Featured Publication Although understanding cells' responses to mechanical stimuli is seen as increasingly important for understanding cell biology, how to best measure, interpret, and model cells' mechanical properties remains unclear. We determine the frequency-dependent she ... Full text Cite

Determining the effect of cytoskeleton disruption on cell rheology

Journal Article AIChE Annual Meeting, Conference Proceedings · December 1, 2005 Understanding cell mechanics is a prerequisite for a detailed understanding of mechano-transduction, which is involved in numerous biological processes such as cell motility and differentiation. Previous studies have shown cells exhibit a power law shear m ... Cite

Polymer physics of the cytoskeleton

Journal Article AIChE Annual Meeting, Conference Proceedings · December 1, 2005 While the importance of mechanics and force in many biological processes is increasingly appreciated, the mechanical response of the cytoskeleton and its physical origin remain poorly understood. In this work we utilize four complimentary techniques to pro ... Cite

Forced unfolding of protein domains determines cytoskeletal rheology

Journal Article AIChE Annual Meeting, Conference Proceedings · December 1, 2005 The importance of mechanics and force to biological processes is increasingly appreciated and has been shown to affect behaviors as distinct as cell motility, morphogenesis, and differentiation. Due to recent advances in microrheological experimental techn ... Cite

Microrheology, stress fluctuations, and active behavior of living cells.

Journal Article Physical review letters · November 2003 We report the first measurements of the intrinsic strain fluctuations of living cells using a recently developed tracer correlation technique along with a theoretical framework for interpreting such data in heterogeneous media with nonthermal driving. The ... Full text Cite

Effects of taxol and Colcemid on myofibrillogenesis.

Journal Article Proceedings of the National Academy of Sciences of the United States of America · November 1982 To determine the relationship between thin filaments, Z-bands, microtubules, intermediate filaments (IFs), T-tubules, and sarcoplasmic reticulum (SR) during myofibrillogenesis, myotubes were selectively depleted of their myofibrils with 12-tetradecanoylpho ... Full text Cite

Effects of taxol and colcemid on myofibrillogenesis

Journal Article Journal of Cell Biology · January 1, 1982 Cite

Reversion from deficiency of galactose-1-phosphate uridylytransferase (GALT) in an SV40-transformed human fibroblast line.

Journal Article Somatic cell genetics · November 1981 Control SV40-transformed human fibroblasts can be readily adapted to growth on medium containing galactose as sole hexose source (galactose-MEH). However, most cells from a line of SV40-transformed skin fibroblasts from a patient with galactosemia (galacto ... Full text Cite