Brenton D. Hoffman
James L. and Elizabeth M. Vincent Associate Professor of Biomedical Engineering
The overall goal of my research program is to utilize an interdisciplinary approach to first advance the basic understanding of mechanotransduction on multiple scales and then use this knowledge to guide the development of new treatments for mechanosensitive diseases. Our work combines principles and techniques from protein engineering, molecular biology, soft matter physics, cell and developmental biology, biomaterials engineering, automated image analysis, and state of the art live cell microscopy. Specifically, we engineer and use biosensors that report the tension across specific proteins in living cells through changes in the color of light they emit. This technology enables dynamic measurements of proteins and sub-cellular structures that are under load. Unlike more traditional techniques that measure the entirety of cellular force output, the ability of these sensors to measure mechanical stress at the molecular level means they are innately compatible with concepts and approaches common in molecular biology and biophysics.
Current Research Interests
Current Appointments & Affiliations
- James L. and Elizabeth M. Vincent Associate Professor of Biomedical Engineering, Biomedical Engineering, Pratt School of Engineering 2020 - 2025
- Associate Professor in the Department of Biomedical Engineering, Biomedical Engineering, Pratt School of Engineering 2020
- Assistant Professor in Cell Biology, Cell Biology, Basic Science Departments 2012
Contact Information
- Background
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Education, Training, & Certifications
- Ph.D., University of Pennsylvania 2007
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Previous Appointments & Affiliations
- Assistant Professor of Biomedical Engineering, Biomedical Engineering, Pratt School of Engineering 2012 - 2019
- Recognition
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In the News
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APR 23, 2020 -
JAN 11, 2016 Duke Research Blog -
JAN 11, 2016 Duke Research Blog -
JAN 28, 2015 -
MAY 30, 2013
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Awards & Honors
- Expertise
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Subject Headings
- Research
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Selected Grants
- University Training Program in Biomolecular and Tissue Engineering awarded by National Institutes of Health 1994 - 2027
- Regulatory Functions of the Differentiated Epidermis awarded by National Institutes of Health 2022 - 2027
- Duke Program of Training in Pulmonary ReSearch to Promote, Engage and Retain Academic Researchers (PROSPER) awarded by National Institutes of Health 2022 - 2026
- Cell and Molecular Biology Training Program awarded by National Institutes of Health 2021 - 2026
- The mechanical role of the glycocalyx in cancer cell adhesion awarded by National Institutes of Health 2020 - 2024
- LUMICKS C-TRAP awarded by National Institutes of Health 2022 - 2023
- Kinesin Force Production and Biomechanics of Division awarded by National Institutes of Health 2021 - 2023
- Molecular Determinants of Confined Migration awarded by Vanderbilt University 2019 - 2023
- Mechanotransduction in Multicellular Systems awarded by National Institutes of Health 2018 - 2022
- EFRI CEE : Engineering Technologies to Determine Causal Relationships Between Chromatin Structure and Gene Regulation awarded by National Science Foundation 2018 - 2022
- Analysis of mechanical induction of bioelectric activity in cells awarded by Army Research Office 2019 - 2022
- CAREER: Force-activated Protein Dynamics in Mechanobiology awarded by National Science Foundation 2015 - 2021
- Visualization of mechanical stress in live cells awarded by National Science Foundation 2016 - 2019
- Visualizing and Elucidating the Role of Force on Type IV Collagen in Development awarded by National Institutes of Health 2016 - 2018
- Elucidating the Role of Mechanosensitive Signaling in Mediating Cell-Biomaterial Interactions awarded by National Institutes of Health 2016 - 2018
- Visualizing and Elucidating Mechanisms of Mechanotransduction in Vascular Smooth Muscle Cells awarded by American Heart Association 2016 - 2018
- Microenvironments for Tendon Tissue Engineering awarded by National Institutes of Health 2014 - 2017
- The Role of Ezrin in Membrane and Actin Interactions awarded by National Institutes of Health 2016 - 2017
- Structural Biology and Biophysics Training Program awarded by National Institutes of Health 1994 - 2015
- Publications & Artistic Works
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Selected Publications
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Academic Articles
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Andress, Benjamin D., Rebecca M. Irwin, Ishaan Puranam, Brenton D. Hoffman, and Amy L. McNulty. “A Tale of Two Loads: Modulation of IL-1 Induced Inflammatory Responses of Meniscal Cells in Two Models of Dynamic Physiologic Loading.” Front Bioeng Biotechnol 10 (2022): 837619. https://doi.org/10.3389/fbioe.2022.837619.Full Text Link to Item
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Menaesse, Audrey, Daniel Sumetsky, Nicolas Emanuely, Jeremy L. Stein, Evan M. Gates, Brenton D. Hoffman, and Nada N. Boustany. “Simplified Instrument Calibration for Wide-Field Fluorescence Resonance Energy Transfer (FRET) Measured by the Sensitized Emission Method.” Cytometry. Part a : The Journal of the International Society for Analytical Cytology 99, no. 4 (April 2021): 407–16. https://doi.org/10.1002/cyto.a.24194.Full Text
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Li, Fenfang, Tae Hyun Park, George Sankin, Christopher Gilchrist, Defei Liao, Chon U. Chan, Zheng Mao, Brenton D. Hoffman, and Pei Zhong. “Mechanically induced integrin ligation mediates intracellular calcium signaling with single pulsating cavitation bubbles.” Theranostics 11, no. 12 (January 2021): 6090–6104. https://doi.org/10.7150/thno.56813.Full Text
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Keeley, Daniel P., Eric Hastie, Ranjay Jayadev, Laura C. Kelley, Qiuyi Chi, Sara G. Payne, Jonathan L. Jeger, Brenton D. Hoffman, and David R. Sherwood. “Comprehensive Endogenous Tagging of Basement Membrane Components Reveals Dynamic Movement within the Matrix Scaffolding.” Developmental Cell 54, no. 1 (July 2020): 60-74.e7. https://doi.org/10.1016/j.devcel.2020.05.022.Full Text
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Dumas, John-Paul, James Y. Jiang, Evan M. Gates, Brenton D. Hoffman, Mark C. Pierce, and Nada N. Boustany. “FRET efficiency measurement in a molecular tension probe with a low-cost frequency-domain fluorescence lifetime imaging microscope.” Journal of Biomedical Optics 24, no. 12 (December 2019): 1–11. https://doi.org/10.1117/1.jbo.24.12.126501.Full Text
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Ham, Trevor R., Kasie L. Collins, and Brenton D. Hoffman. “Molecular Tension Sensors: Moving Beyond Force.” Current Opinion in Biomedical Engineering 12 (December 2019): 83–94. https://doi.org/10.1016/j.cobme.2019.10.003.Full Text
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Mosier, Jenna A., Aniqua Rahman-Zaman, Matthew R. Zanotelli, Jacob A. VanderBurgh, Francois Bordeleau, Brenton D. Hoffman, and Cynthia A. Reinhart-King. “Extent of Cell Confinement in Microtracks Affects Speed and Results in Differential Matrix Strains.” Biophysical Journal 117, no. 9 (November 2019): 1692–1701. https://doi.org/10.1016/j.bpj.2019.09.024.Full Text
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Sengupta, Swarnali, Katheryn E. Rothenberg, Hanjun Li, Brenton D. Hoffman, and Nenad Bursac. “Altering integrin engagement regulates membrane localization of Kir2.1 channels.” Journal of Cell Science 132, no. 17 (September 2019): jcs225383. https://doi.org/10.1242/jcs.225383.Full Text
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Gilchrist, Christopher L., Holly A. Leddy, Laurel Kaye, Natasha D. Case, Katheryn E. Rothenberg, Dianne Little, Wolfgang Liedtke, Brenton D. Hoffman, and Farshid Guilak. “TRPV4-mediated calcium signaling in mesenchymal stem cells regulates aligned collagen matrix formation and vinculin tension.” Proc Natl Acad Sci U S A 116, no. 6 (February 5, 2019): 1992–97. https://doi.org/10.1073/pnas.1811095116.Full Text Link to Item
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Gates, Evan M., Andrew S. LaCroix, Katheryn E. Rothenberg, and Brenton D. Hoffman. “Improving Quality, Reproducibility, and Usability of FRET-Based Tension Sensors.” Cytometry. Part a : The Journal of the International Society for Analytical Cytology 95, no. 2 (February 2019): 201–13. https://doi.org/10.1002/cyto.a.23688.Full Text
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Rothenberg, Katheryn E., Ishaan Puranam, and Brenton D. Hoffman. “Measurement of Force-Sensitive Protein Dynamics in Living Cells Using a Combination of Fluorescent Techniques.” Journal of Visualized Experiments : Jove, no. 141 (November 2018). https://doi.org/10.3791/58619.Full Text
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LaCroix, Andrew S., Andrew D. Lynch, Matthew E. Berginski, and Brenton D. Hoffman. “Tunable molecular tension sensors reveal extension-based control of vinculin loading.” Elife 7 (July 2018): e33927. https://doi.org/10.7554/elife.33927.Full Text
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Rothenberg, Katheryn E., David W. Scott, Nicolas Christoforou, and Brenton D. Hoffman. “Vinculin Force-Sensitive Dynamics at Focal Adhesions Enable Effective Directed Cell Migration.” Biophysical Journal 114, no. 7 (April 2018): 1680–94. https://doi.org/10.1016/j.bpj.2018.02.019.Full Text
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Graham, David M., Tomas Andersen, Lisa Sharek, Gunes Uzer, Katheryn Rothenberg, Brenton D. Hoffman, Janet Rubin, Martial Balland, James E. Bear, and Keith Burridge. “Enucleated cells reveal differential roles of the nucleus in cell migration, polarity, and mechanotransduction.” The Journal of Cell Biology 217, no. 3 (March 2018): 895–914. https://doi.org/10.1083/jcb.201706097.Full Text
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Shams, Hengameh, Brenton D. Hoffman, and Mohammad R. K. Mofrad. “The "Stressful" Life of Cell Adhesion Molecules: On the Mechanosensitivity of Integrin Adhesome.” Journal of Biomechanical Engineering 140, no. 2 (February 2018). https://doi.org/10.1115/1.4038812.Full Text
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Mao, Mao, Liangli Wang, Chun-Chi Chang, Katheryn E. Rothenberg, Jianyong Huang, Yingxiao Wang, Brenton D. Hoffman, Paloma B. Liton, and Fan Yuan. “Involvement of a Rac1-Dependent Macropinocytosis Pathway in Plasmid DNA Delivery by Electrotransfection.” Molecular Therapy : The Journal of the American Society of Gene Therapy 25, no. 3 (March 2017): 803–15. https://doi.org/10.1016/j.ymthe.2016.12.009.Full Text
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Pomeroy, Jordan E., Hung X. Nguyen, Brenton D. Hoffman, and Nenad Bursac. “Genetically Encoded Photoactuators and Photosensors for Characterization and Manipulation of Pluripotent Stem Cells.” Theranostics 7, no. 14 (2017): 3539–58. https://doi.org/10.7150/thno.20593.Full Text Open Access Copy Link to Item
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Hoffman, Brenton D., and Alpha S. Yap. “Towards a Dynamic Understanding of Cadherin-Based Mechanobiology.” Trends in Cell Biology 25, no. 12 (December 2015): 803–14. https://doi.org/10.1016/j.tcb.2015.09.008.Full Text
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Rothenberg, K. E., S. S. Neibart, A. S. LaCroix, and B. D. Hoffman. “Controlling Cell Geometry Affects the Spatial Distribution of Load Across Vinculin.” Cellular and Molecular Bioengineering 8, no. 3 (September 21, 2015): 364–82. https://doi.org/10.1007/s12195-015-0404-9.Full Text
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LaCroix, Andrew S., Katheryn E. Rothenberg, and Brenton D. Hoffman. “Molecular-Scale Tools for Studying Mechanotransduction.” Annual Review of Biomedical Engineering 17 (January 2015): 287–316. https://doi.org/10.1146/annurev-bioeng-071114-040531.Full Text
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LaCroix, Andrew S., Katheryn E. Rothenberg, Matthew E. Berginski, Aarti N. Urs, and Brenton D. Hoffman. “Construction, imaging, and analysis of FRET-based tension sensors in living cells.” Methods in Cell Biology 125 (January 2015): 161–86. https://doi.org/10.1016/bs.mcb.2014.10.033.Full Text
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Yan, Chao, Degang Liu, Liwei Li, Michael F. Wempe, Sunny Guin, May Khanna, Jeremy Meier, et al. “Discovery and characterization of small molecules that target the GTPase Ral.” Nature 515, no. 7527 (November 2014): 443–47. https://doi.org/10.1038/nature13713.Full Text
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Leerberg, Joanne M., Guillermo A. Gomez, Suzie Verma, Elliott J. Moussa, Selwin K. Wu, Rashmi Priya, Brenton D. Hoffman, Carsten Grashoff, Martin A. Schwartz, and Alpha S. Yap. “Tension-sensitive actin assembly supports contractility at the epithelial zonula adherens.” Current Biology : Cb 24, no. 15 (August 2014): 1689–99. https://doi.org/10.1016/j.cub.2014.06.028.Full Text
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Moissoglu, Konstadinos, Volker Kiessling, Chen Wan, Brenton D. Hoffman, Andres Norambuena, Lukas K. Tamm, and Martin Alexander Schwartz. “Regulation of Rac1 translocation and activation by membrane domains and their boundaries.” Journal of Cell Science 127, no. Pt 11 (June 2014): 2565–76. https://doi.org/10.1242/jcs.149088.Full Text
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Hwang, Priscilla Y., Jun Chen, Liufang Jing, Brenton D. Hoffman, and Lori A. Setton. “The role of extracellular matrix elasticity and composition in regulating the nucleus pulposus cell phenotype in the intervertebral disc: a narrative review.” Journal of Biomechanical Engineering 136, no. 2 (February 2014): 021010. https://doi.org/10.1115/1.4026360.Full Text Open Access Copy
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Hoffman, Brenton D. “The detection and role of molecular tension in focal adhesion dynamics.” Progress in Molecular Biology and Translational Science 126 (January 2014): 3–24. https://doi.org/10.1016/b978-0-12-394624-9.00001-4.Full Text
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Ellis, Kathryn, Brenton D. Hoffman, and Michel Bagnat. “The vacuole within: how cellular organization dictates notochord function.” Bioarchitecture 3, no. 3 (2013): 64–68. https://doi.org/10.4161/bioa.25503.Full Text Link to Item
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Goguen, B. N., B. D. Hoffman, J. R. Sellers, M. A. Schwartz, and B. Imperiali. “Light-Triggered Myosin Activation for Probing Dynamic Cellular Processes.” Angewandte Chemie International Edition 50, no. 25 (2011): 5666–69.
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Hoffman, B. D., C. Grashoff, and M. A. Schwartz. “Dynamic molecular processes mediate cellular mechanotransduction.” Nature 475, no. 7356 (2011): 316–23. https://doi.org/10.1038/nature10316.Full Text
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Eucker, Stephanie A., Brenton D. Hoffman, Rahul Natesh, Jill Ralston, William M. Armstead, and Susan S. Margulies. “Development of a fluorescent microsphere technique for rapid histological determination of cerebral blood flow.” Brain Res 1326 (April 22, 2010): 128–34. https://doi.org/10.1016/j.brainres.2010.02.059.Full Text Link to Item
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Grashoff, C., B. D. Hoffman, M. D. Brenner, R. Zhou, M. Parsons, M. T. Yang, M. A. McLean, et al. “Measuring mechanical tension across vinculin reveals regulation of focal adhesion dynamics.” Nature 466, no. 7303 (2010): 263–66. https://doi.org/10.1038/nature09198.Full Text
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Hoffman, Brenton D., and John C. Crocker. “Cell mechanics: dissecting the physical responses of cells to force.” Annual Review of Biomedical Engineering 11 (January 2009): 259–88. https://doi.org/10.1146/annurev.bioeng.10.061807.160511.Full Text
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Hoffman, Brenton D., Gladys Massiera, and John C. Crocker. “Fragility and mechanosensing in a thermalized cytoskeleton model with forced protein unfolding.” Physical Review. E, Statistical, Nonlinear, and Soft Matter Physics 76, no. 5 Pt 1 (November 2007): 051906. https://doi.org/10.1103/physreve.76.051906.Full Text
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Crocker, John C., and Brenton D. Hoffman. “Multiple-particle tracking and two-point microrheology in cells.” Methods in Cell Biology 83 (January 2007): 141–78. https://doi.org/10.1016/s0091-679x(07)83007-x.Full Text
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Van Citters, Kathleen M., Brenton D. Hoffman, Gladys Massiera, and John C. Crocker. “The role of F-actin and myosin in epithelial cell rheology.” Biophysical Journal 91, no. 10 (November 2006): 3946–56. https://doi.org/10.1529/biophysj.106.091264.Full Text
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Byfield, F. J., B. D. Hoffman, V. G. Romanenko, Y. Fang, J. C. Crocker, and I. Levitan. “Evidence for the role of cell stiffness in modulation of volume-regulated anion channels.” Acta Physiologica (Oxford, England) 187, no. 1–2 (May 2006): 285–94. https://doi.org/10.1111/j.1748-1716.2006.01555.x.Full Text
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Liu, J., M. L. Gardel, K. Kroy, E. Frey, B. D. Hoffman, J. C. Crocker, A. R. Bausch, and D. A. Weitz. “Microrheology probes length scale dependent rheology.” Physical Review Letters 96, no. 11 (March 2006): 118104. https://doi.org/10.1103/physrevlett.96.118104.Full Text
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Hoffman, B. D., G. Massiera, K. M. V. Citters, and J. C. Crocker. “The consensus mechanics of cultured mammalian cells.” Proceedings of the National Academy of Sciences of the United States of America 103, no. 27 (2006): 10259–64. https://doi.org/10.1073/pnas.0510348103.Full Text
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Hoffman, B. D., G. Massiera, K. Miranda, and J. Crocker. “Polymer physics of the cytoskeleton.” Aiche Annual Meeting, Conference Proceedings, December 1, 2005, 181.
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Hoffman, B., G. Massiera, and J. Cracker. “Forced unfolding of protein domains determines cytoskeletal rheology.” Aiche Annual Meeting, Conference Proceedings, December 1, 2005, 1140.
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Miranda, K., B. D. Hoffman, G. Massiera, and J. Crocker. “Determining the effect of cytoskeleton disruption on cell rheology.” Aiche Annual Meeting, Conference Proceedings, December 1, 2005, 5021.
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Lau, A. W., B. D. Hoffman, A. Davies, J. C. Crocker, and T. C. Lubensky. “Microrheology, stress fluctuations, and active behavior of living cells.” Physical Review Letters 91, no. 19 (November 2003): 198101. https://doi.org/10.1103/physrevlett.91.198101.Full Text
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Toyama, Y., S. Forry-Schaudies, B. Hoffman, and H. Holtzer. “Effects of taxol and Colcemid on myofibrillogenesis.” Proceedings of the National Academy of Sciences of the United States of America 79, no. 21 (November 1982): 6556–60. https://doi.org/10.1073/pnas.79.21.6556.Full Text
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Forry-Schaudies, S., Y. Toyama, B. Hoffman, and H. Holtzer. “Effects of taxol and colcemid on myofibrillogenesis.” Journal of Cell Biology 95, no. 2 II (January 1, 1982).
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Benn, P. A., R. I. Kelley, W. J. Mellman, L. Amer, F. S. Boches, H. B. Markus, W. Nichols, and B. Hoffman. “Reversion from deficiency of galactose-1-phosphate uridylytransferase (GALT) in an SV40-transformed human fibroblast line.” Somatic Cell Genetics 7, no. 6 (November 1981): 667–82. https://doi.org/10.1007/bf01538756.Full Text
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Book Sections
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Collins, K. L., E. M. Gates, C. L. Gilchrist, and B. D. Hoffman. “Bio-Instructive Cues in Scaffolds for Musculoskeletal Tissue Engineering and Regenerative Medicine.” In Bio-Instructive Scaffolds for Musculoskeletal Tissue Engineering and Regenerative Medicine, 3–35, 2017. https://doi.org/10.1016/B978-0-12-803394-4.00001-X.Full Text
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Conference Papers
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Highland, T., S. M. Parker, H. Price, M. Reynolds, S. He, B. D. Hoffman, and A. Wax. “Combined Quantitative Phase Microscopy and Förster Resonance Energy Transfer Imaging for Analyzing Endothelial Cell Shear Stress Response.” In Optics Infobase Conference Papers, 2022.
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Parker, S. M., H. Price, M. Reynolds, S. He, B. D. Hoffman, and A. Wax. “Combined quantitative phase microscopy and förster resonance energy transfer for analyzing cell ion dynamics.” In Optics Infobase Conference Papers, 2021.
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Dumas, J. P., J. Y. Jiang, E. M. Gates, B. D. Hoffman, M. C. Pierce, and N. N. Boustany. “FRET efficiency measurement with a low-cost frequency domain fluorescence lifetime imaging microscope.” In Optics Infobase Conference Papers, Vol. Part F177-Microscopy-2020, 2020. https://doi.org/10.1364/MICROSCOPY.2020.MTu4A.7.Full Text
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Hoffman, B. D., K. A. Miranda, G. Massiera, and J. C. Crocker. “Cytoskeletal rheology and forced unfolding of cross-link protein domains.” In Biophysical Journal, 88:493A-493A. BIOPHYSICAL SOCIETY, 2005.Link to Item
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Miranda, K. A., B. D. Hoffman, G. Massiera, and J. C. Crocker. “Measuring cytoskeleton mechanics and its relationship to the actin model.” In Biophysical Journal, 88:493A-493A. BIOPHYSICAL SOCIETY, 2005.Link to Item
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Crocker, J. C., B. D. Hoffman, G. Massiera, and K. Miranda. “Rheology and strain fluctuations in living cells: Implications for cell mechanics.” In Biophysical Journal, 86:59A-59A. BIOPHYSICAL SOCIETY, 2004.Link to Item
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Hoffman, B. D., A. W. C. Lau, T. Lubensky, and J. Crocker. “Investigating stress and strain fluctuations in the living cytoskeleton.” In Biophysical Journal, 86:60A-60A. BIOPHYSICAL SOCIETY, 2004.Link to Item
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- Teaching & Mentoring
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Recent Courses
- BME 306L: Cellular Engineering (AC or GE) 2023
- BME 394: Projects in Biomedical Engineering (GE) 2023
- BME 493: Projects in Biomedical Engineering (GE) 2023
- BME 791: Graduate Independent Study 2023
- EGR 393: Research Projects in Engineering 2023
- BME 390L: Special Topics with a Lab 2022
- BME 494: Projects in Biomedical Engineering (GE) 2022
- BME 527: Cell Mechanics and Mechanotransduction (GE, BB, MC) 2022
- BME 711S: Biological Engineering Seminar Series (CBIMMS and CBTE) 2022
- BME 712S: Biological Engineering Seminar Series (CBIMMS and CBTE) 2022
- ME 391: Undergraduate Projects in Mechanical Engineering 2022
- ME 717S: Biological Engineering Seminar Series (CBIMMS and CBTE) 2022
- ME 718S: Biological Engineering Seminar Series (CBIMMS and CBTE) 2022
- BME 302L: Fundamentals of Biomaterials and Biomechanics (AC or GE) 2021
- BME 394: Projects in Biomedical Engineering (GE) 2021
- BME 493: Projects in Biomedical Engineering (GE) 2021
- BME 494: Projects in Biomedical Engineering (GE) 2021
- BME 527: Cell Mechanics and Mechanotransduction (GE, BB, MC) 2021
- BME 711S: Biological Engineering Seminar Series (CBIMMS and CBTE) 2021
- BME 712S: Biological Engineering Seminar Series (CBIMMS and CBTE) 2021
- BME 791: Graduate Independent Study 2021
- BME 792: Continuation of Graduate Independent Study 2021
- ME 717S: Biological Engineering Seminar Series (CBIMMS and CBTE) 2021
- ME 718S: Biological Engineering Seminar Series (CBIMMS and CBTE) 2021
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