Brenton D. Hoffman

Research Interests

Focused on understanding, on a molecular level, how mechanical and chemical cues from the environment are detected, integrated, and manipulated by cells to dictate physiological and patho-physiological responses important in vascular biology.

Bio

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.

Education

• Ph.D. University of Pennsylvania, 2007

Positions

• James L. and Elizabeth M. Vincent Associate Professor of Biomedical Engineering
• Associate Professor in the Department of Biomedical Engineering
• Assistant Professor in Cell Biology

Awards, Honors, and Distinctions

• Klein Family Distinguished Teaching Award. Pratt School of Engineering. 2016
• Scholars. Searle Scholars. 2013

Courses Taught

• ME 718S: Biological Engineering Seminar Series (CBIMMS and CBTE)
• ME 717S: Biological Engineering Seminar Series (CBIMMS and CBTE)
• ME 391: Undergraduate Projects in Mechanical Engineering
• EGR 393: Research Projects in Engineering
• BME 792: Continuation of Graduate Independent Study
• BME 791: Graduate Independent Study
• BME 712S: Biological Engineering Seminar Series (CBIMMS and CBTE)
• BME 711S: Biological Engineering Seminar Series (CBIMMS and CBTE)
• BME 527: Cell Mechanics and Mechanotransduction (GE, BB, MC)
• BME 494: Projects in Biomedical Engineering (GE)
• BME 493: Projects in Biomedical Engineering (GE)
• BME 394: Projects in Biomedical Engineering (GE)
• BME 390L: Special Topics with a Lab
• BME 306L: Cellular Engineering (AC or GE)

Publications

• Highland RE, Rancu A, Price H, Parker SM, Reynolds M, Hoffman BD, et al. Multimodal segmentation of dynamic subcellular features using quantitative phase imaging and FRET-based sensors [Invited]. Journal of the Optical Society of America A: Optics and Image Science, and Vision. 2024 Nov 1;41(11):C38–48.
• Shoyer TC, Collins KL, Ham TR, Blanchard AT, Malavade JN, Johns BA, et al. Detection of fluorescent protein mechanical switching in cellulo. Cell reports methods. 2024 Jul;4(7):100815.
• Chirasani VR, Khan MAI, Malavade JN, Dokholyan NV, Hoffman BD, Campbell SL. Molecular basis and cellular functions of vinculin-actin directional catch bonding. Nature communications. 2023 Dec;14(1):8300.
• Shoyer TC, Gates EM, Cabe JI, Urs AN, Conway DE, Hoffman BD. Coupling during collective cell migration is controlled by a vinculin mechanochemical switch. Proceedings of the National Academy of Sciences of the United States of America. 2023 Dec;120(50):e2316456120.
• Tao A, LaCroix AS, Shoyer TC, Venkatraman V, Xu KL, Feiger B, et al. Identifying constitutive and context-specific molecular-tension-sensitive protein recruitment within focal adhesions. Developmental cell. 2023 Mar;58(6):522-534.e7.
• Andress BD, Irwin RM, Puranam I, Hoffman BD, McNulty AL. 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. 2022;10:837619.
• Highland T, Parker SM, Price H, Reynolds M, He S, Hoffman BD, et al. Combined Quantitative Phase Microscopy and Förster Resonance Energy Transfer Imaging for Analyzing Endothelial Cell Shear Stress Response. In: Optics InfoBase Conference Papers. 2022.
• Menaesse A, Sumetsky D, Emanuely N, Stein JL, Gates EM, Hoffman BD, et al. 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. 2021 Apr;99(4):407–16.
• Li F, Park TH, Sankin G, Gilchrist C, Liao D, Chan CU, et al. Mechanically induced integrin ligation mediates intracellular calcium signaling with single pulsating cavitation bubbles. Theranostics. 2021 Jan;11(12):6090–104.
• Parker SM, Price H, Reynolds M, He S, Hoffman BD, Wax A. Combined quantitative phase microscopy and förster resonance energy transfer for analyzing cell ion dynamics. In: Optics InfoBase Conference Papers. 2021.
• Keeley DP, Hastie E, Jayadev R, Kelley LC, Chi Q, Payne SG, et al. Comprehensive Endogenous Tagging of Basement Membrane Components Reveals Dynamic Movement within the Matrix Scaffolding. Developmental cell. 2020 Jul;54(1):60-74.e7.
• Dumas JP, Jiang JY, Gates EM, Hoffman BD, Pierce MC, Boustany NN. FRET efficiency measurement with a low-cost frequency domain fluorescence lifetime imaging microscope. In: Optics InfoBase Conference Papers. 2020.
• Ham TR, Collins KL, Hoffman BD. Molecular Tension Sensors: Moving Beyond Force. Current opinion in biomedical engineering. 2019 Dec;12:83–94.
• Dumas J-P, Jiang JY, Gates EM, Hoffman BD, Pierce MC, Boustany NN. FRET efficiency measurement in a molecular tension probe with a low-cost frequency-domain fluorescence lifetime imaging microscope. Journal of biomedical optics. 2019 Dec;24(12):1–11.
• Mosier JA, Rahman-Zaman A, Zanotelli MR, VanderBurgh JA, Bordeleau F, Hoffman BD, et al. Extent of Cell Confinement in Microtracks Affects Speed and Results in Differential Matrix Strains. Biophysical journal. 2019 Nov;117(9):1692–701.
• Sengupta S, Rothenberg KE, Li H, Hoffman BD, Bursac N. Altering integrin engagement regulates membrane localization of K_ir2.1 channels. Journal of cell science. 2019 Sep;132(17):jcs225383.
• Gilchrist CL, Leddy HA, Kaye L, Case ND, Rothenberg KE, Little D, et al. TRPV4-mediated calcium signaling in mesenchymal stem cells regulates aligned collagen matrix formation and vinculin tension. Proc Natl Acad Sci U S A. 2019 Feb 5;116(6):1992–7.
• Gates EM, LaCroix AS, Rothenberg KE, Hoffman BD. Improving Quality, Reproducibility, and Usability of FRET-Based Tension Sensors. Cytometry Part A : the journal of the International Society for Analytical Cytology. 2019 Feb;95(2):201–13.
• Rothenberg KE, Puranam I, Hoffman BD. Measurement of Force-Sensitive Protein Dynamics in Living Cells Using a Combination of Fluorescent Techniques. Journal of visualized experiments : JoVE. 2018 Nov;(141).
• LaCroix AS, Lynch AD, Berginski ME, Hoffman BD. Tunable molecular tension sensors reveal extension-based control of vinculin loading. eLife. 2018 Jul;7:e33927.
• Rothenberg KE, Scott DW, Christoforou N, Hoffman BD. Vinculin Force-Sensitive Dynamics at Focal Adhesions Enable Effective Directed Cell Migration. Biophysical journal. 2018 Apr;114(7):1680–94.
• Graham DM, Andersen T, Sharek L, Uzer G, Rothenberg K, Hoffman BD, et al. Enucleated cells reveal differential roles of the nucleus in cell migration, polarity, and mechanotransduction. The Journal of cell biology. 2018 Mar;217(3):895–914.
• Shams H, Hoffman BD, Mofrad MRK. The "Stressful" Life of Cell Adhesion Molecules: On the Mechanosensitivity of Integrin Adhesome. Journal of biomechanical engineering. 2018 Feb;140(2).
• Mao M, Wang L, Chang C-C, Rothenberg KE, Huang J, Wang Y, et al. Involvement of a Rac1-Dependent Macropinocytosis Pathway in Plasmid DNA Delivery by Electrotransfection. Mol Ther. 2017 Mar 1;25(3):803–15.
• Collins KL, Gates EM, Gilchrist CL, Hoffman BD. Bio-Instructive Cues in Scaffolds for Musculoskeletal Tissue Engineering and Regenerative Medicine. In: Bio-Instructive Scaffolds for Musculoskeletal Tissue Engineering and Regenerative Medicine. 2017. p. 3–35.
• Pomeroy JE, Nguyen HX, Hoffman BD, Bursac N. Genetically Encoded Photoactuators and Photosensors for Characterization and Manipulation of Pluripotent Stem Cells. Theranostics. 2017;7(14):3539–58.
• Hoffman BD, Yap AS. Towards a Dynamic Understanding of Cadherin-Based Mechanobiology. Trends in cell biology. 2015 Dec;25(12):803–14.
• Rothenberg KE, Neibart SS, LaCroix AS, Hoffman BD. Controlling Cell Geometry Affects the Spatial Distribution of Load Across Vinculin. Cellular and Molecular Bioengineering. 2015 Sep 21;8(3):364–82.
• LaCroix AS, Rothenberg KE, Hoffman BD. Molecular-Scale Tools for Studying Mechanotransduction. Annual review of biomedical engineering. 2015 Jan;17:287–316.
• LaCroix AS, Rothenberg KE, Berginski ME, Urs AN, Hoffman BD. Construction, imaging, and analysis of FRET-based tension sensors in living cells. Methods in cell biology. 2015 Jan;125:161–86.
• Yan C, Liu D, Li L, Wempe MF, Guin S, Khanna M, et al. Discovery and characterization of small molecules that target the GTPase Ral. Nature. 2014 Nov;515(7527):443–7.
• Leerberg JM, Gomez GA, Verma S, Moussa EJ, Wu SK, Priya R, et al. Tension-sensitive actin assembly supports contractility at the epithelial zonula adherens. Current biology : CB. 2014 Aug;24(15):1689–99.
• Moissoglu K, Kiessling V, Wan C, Hoffman BD, Norambuena A, Tamm LK, et al. Regulation of Rac1 translocation and activation by membrane domains and their boundaries. Journal of cell science. 2014 Jun;127(Pt 11):2565–76.
• Hwang PY, Chen J, Jing L, Hoffman BD, Setton LA. 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. 2014 Feb;136(2):021010.
• Hoffman BD. The detection and role of molecular tension in focal adhesion dynamics. Progress in molecular biology and translational science. 2014 Jan;126:3–24.
• Ellis K, Hoffman BD, Bagnat M. The vacuole within: how cellular organization dictates notochord function. Bioarchitecture. 2013;3(3):64–8.
• Hoffman BD, Grashoff C, Schwartz MA. Dynamic molecular processes mediate cellular mechanotransduction. Nature. 2011;475(7356):316–23.
• Goguen BN, Hoffman BD, Sellers JR, Schwartz MA, Imperiali B. Light-Triggered Myosin Activation for Probing Dynamic Cellular Processes. Angewandte Chemie-International Edition. 2011;50(25):5666–9.
• Eucker SA, Hoffman BD, Natesh R, Ralston J, Armstead WM, Margulies SS. Development of a fluorescent microsphere technique for rapid histological determination of cerebral blood flow. Brain Res. 2010 Apr 22;1326:128–34.
• Grashoff C, Hoffman BD, Brenner MD, Zhou R, Parsons M, Yang MT, et al. Measuring mechanical tension across vinculin reveals regulation of focal adhesion dynamics. Nature. 2010;466(7303):263–6.
• Hoffman BD, Crocker JC. Cell mechanics: dissecting the physical responses of cells to force. Annual review of biomedical engineering. 2009 Jan;11:259–88.
• Hoffman BD, Massiera G, Crocker JC. Fragility and mechanosensing in a thermalized cytoskeleton model with forced protein unfolding. Physical review E, Statistical, nonlinear, and soft matter physics. 2007 Nov;76(5 Pt 1):051906.
• Crocker JC, Hoffman BD. Multiple-particle tracking and two-point microrheology in cells. Methods in cell biology. 2007 Jan;83:141–78.
• Van Citters KM, Hoffman BD, Massiera G, Crocker JC. The role of F-actin and myosin in epithelial cell rheology. Biophysical journal. 2006 Nov;91(10):3946–56.
• Byfield FJ, Hoffman BD, Romanenko VG, Fang Y, Crocker JC, Levitan I. Evidence for the role of cell stiffness in modulation of volume-regulated anion channels. Acta physiologica (Oxford, England). 2006 May;187(1–2):285–94.
• Liu J, Gardel ML, Kroy K, Frey E, Hoffman BD, Crocker JC, et al. Microrheology probes length scale dependent rheology. Physical review letters. 2006 Mar;96(11):118104.
• Hoffman BD, Massiera G, Citters KMV, Crocker JC. The consensus mechanics of cultured mammalian cells. Proceedings of the National Academy of Sciences of the United States of America. 2006;103(27):10259–64.
• Miranda K, Hoffman BD, Massiera G, Crocker J. Determining the effect of cytoskeleton disruption on cell rheology. AIChE Annual Meeting, Conference Proceedings. 2005 Dec 1;5021.
• Hoffman BD, Massiera G, Miranda K, Crocker J. Polymer physics of the cytoskeleton. AIChE Annual Meeting, Conference Proceedings. 2005 Dec 1;181.
• Hoffman B, Massiera G, Cracker J. Forced unfolding of protein domains determines cytoskeletal rheology. AIChE Annual Meeting, Conference Proceedings. 2005 Dec 1;1140.
• Miranda KA, Hoffman BD, Massiera G, Crocker JC. Measuring cytoskeleton mechanics and its relationship to the actin model. In: BIOPHYSICAL JOURNAL. BIOPHYSICAL SOCIETY; 2005. p. 493A-493A.
• Hoffman BD, Miranda KA, Massiera G, Crocker JC. Cytoskeletal rheology and forced unfolding of cross-link protein domains. In: BIOPHYSICAL JOURNAL. BIOPHYSICAL SOCIETY; 2005. p. 493A-493A.
• Crocker JC, Hoffman BD, Massiera G, Miranda K. Rheology and strain fluctuations in living cells: Implications for cell mechanics. In: BIOPHYSICAL JOURNAL. BIOPHYSICAL SOCIETY; 2004. p. 59A-59A.
• Hoffman BD, Lau AWC, Lubensky T, Crocker J. Investigating stress and strain fluctuations in the living cytoskeleton. In: BIOPHYSICAL JOURNAL. BIOPHYSICAL SOCIETY; 2004. p. 60A-60A.
• Lau AWC, Hoffman BD, Davies A, Crocker JC, Lubensky TC. Microrheology, stress fluctuations, and active behavior of living cells. Physical review letters. 2003 Nov;91(19):198101.
• Toyama Y, Forry-Schaudies S, Hoffman B, Holtzer H. Effects of taxol and Colcemid on myofibrillogenesis. Proceedings of the National Academy of Sciences of the United States of America. 1982 Nov;79(21):6556–60.
• Forry-Schaudies S, Toyama Y, Hoffman B, Holtzer H. Effects of taxol and colcemid on myofibrillogenesis. Journal of Cell Biology. 1982 Jan 1;95(2 II).
• Benn PA, Kelley RI, Mellman WJ, Amer L, Boches FS, Markus HB, et al. Reversion from deficiency of galactose-1-phosphate uridylytransferase (GALT) in an SV40-transformed human fibroblast line. Somatic cell genetics. 1981 Nov;7(6):667–82.

In The News

• Five New Bass Professors Named for Excellence in Teaching and Research (Apr 23, 2020 | )
• Measuring the Mechanical Forces of Disease (Jan 11, 2016 | Duke Research Blog)
• Brenton Hoffman Wins National Science Foundation Early CAREER Award (Jan 28, 2015 | )
• Hoffman Wins Two Prizes for Young Investigators (May 30, 2013 | )