Because the cardiovascular system has a fundamental mechanical role, almost all cardiovascular pathophysiologic conditions have important mechanical factors or consequences. In some circumstances, mechanical parameters are the primary initiators of the pathophysiologic processes. For example, hypertension, irrespective of its etiology may lead to arterial sclerosis. Similarly, sustained mechanical overload leads to left ventricular hypertrophy and eventual myocardial decompensation. In other circumstances, the influence of mechanical forces may be more subtle but just as clinical. For example, atherogenesis is associated with regions of disturbed flow due to changes in endothelial cell phenotype. Furthermore, we now recognized atherosclerotic plaque mechanical forces as critical determinants in lesion stability. The central theme of this Program is that mechanical forces are fundamental regulator of molecular events in the cardiovascular system because the cell functions as an integrator of mechanical and biochemical signals to provide the overall molecular response. We propose that while some mechanisms of mechanotransfuction may be ubiquitous, the ultimate molecular responses may be specific to the differentiated cell and the nature of the specific mechanical signal. The goal of this Program is to close the gap between bioengineering and cell biology by interfacing fundamental studies of mechanotransduction with studies of highly differentiated cellular responses that are directly relevant to cardiovascular diseases. In order to address important questions in this emerging area, it is essential to have state-of-the-art techniques for studying the responses of cells to mechanical stimuli. We have assembled a multi-disciplinary team of investigators with established records of independent investigation as well as collaboration. In a series of four interrelated Projects and three Core laboratories, we will employ a spectrum of tools to study mechanotransduction.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Program Projects (P01)
Project #
Application #
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Program Officer
Lundberg, Martha
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Massachusetts Institute of Technology
Biomedical Engineering
Schools of Arts and Sciences
United States
Zip Code
Rahim, Nur Aida Adbul; Pelet, Serge; Kamm, Roger D et al. (2012) Methodological considerations for global analysis of cellular FLIM/FRET measurements. J Biomed Opt 17:026013
Chung, Euiheon; Kim, Yang-Hyo; Tang, Wai Teng et al. (2009) Wide-field extended-resolution fluorescence microscopy with standing surface-plasmon-resonance waves. Opt Lett 34:2366-8
Jonas, Maxine; Huang, Hayden; Kamm, Roger D et al. (2008) Fast fluorescence laser tracking microrheometry. I: instrument development. Biophys J 94:1459-69
Jonas, Maxine; Huang, Hayden; Kamm, Roger D et al. (2008) Fast fluorescence laser tracking microrheometry, II: quantitative studies of cytoskeletal mechanotransduction. Biophys J 95:895-909
Ferrer, Jorge M; Lee, Hyungsuk; Chen, Jiong et al. (2008) Measuring molecular rupture forces between single actin filaments and actin-binding proteins. Proc Natl Acad Sci U S A 105:9221-6
Previte, Michael J R; Pelet, Serge; Kim, Ki Hean et al. (2008) Spectrally resolved fluorescence correlation spectroscopy based on global analysis. Anal Chem 80:3277-84
Lee, S E; Chunsrivirot, S; Kamm, R D et al. (2008) Molecular dynamics study of talin-vinculin binding. Biophys J 95:2027-36
Jonas, Maxine; So, Peter T C; Huang, Hayden (2008) Cell mechanics at multiple scales. Methods Enzymol 443:177-98
Ji, Julie Y; Lee, Richard T; Vergnes, Laurent et al. (2007) Cell nuclei spin in the absence of lamin b1. J Biol Chem 282:20015-26
Norton, G V; Novarini, J C (2007) Modeling ultrasonic transient scattering from biological tissues including their dispersive properties directly in the time domain. Mol Cell Biomech 4:75-85

Showing the most recent 10 out of 43 publications