Roger Kamm, Ph.D.
Department of Biological Engineering Division
Germeshausen Professor of Mechanical & Biological Engineering
Associate Director for Programs, Center for Biomedical Engineering
Ph.D. Mechanical Engineering, 1977
Massachusetts Institute of Technology
The primary research objective of the Kamm laboratory is the application of fundamentals in fluid and solid mechanics to better understand essential biological and physiological phenomena. Our current work is focused on two areas: 1) molecular mechanisms of cellular force sensation; and 2) development of new scaffold materials for vascularized engineered tissues.
Molecular mechanisms of cellular force sensation
It is known that physical forces play an essential role in a variety of tissues and disease processes. For example, endothelial cells in arteries respond to shear stress from blood flow. This response contributes to the pathogenesis of atherosclerosis and to the initiation of an inflammatory response that accompanies late-stage disease. We are developing models of cellular biomechanics and mechanotransduction, the generation of a biochemical signal from a physical stimulus using empirical biology both to generate data for the models and for model validation. Ultimately, this information will be central to the development of treatment strategies that can slow or even reverse the progression of disease.
One approach is to model whole-cell responses by using finite element analysis to determine the mechanisms of force transmission throughout the cell and the magnitudes of internal stress. For example, we simulate experiments conducted in our laboratory in which magnetic beads are tethered to the cell surface, forces are applied, and the cellular response is monitored. We also simulate cellular deformations that result from the application of shear stress caused by the flow of blood over the surface of endothelial cells. Such stresses are transmitted via an interconnected network of proteins, many of which are candidate molecular sensors.
On a finer scale, molecular dynamic simulations are used to develop single-molecule models for proteins that are suspected to be involved in mechanotransduction. Cell surface stimulation activates several proteins in the focal adhesion complex, acting primarily through integrin transmembrane proteins. Forces acting on these cell surface proteins and transmitted to the cytoskeleton and to other, more remote regions of the cell, cause conformational changes that may alter binding affinity for other intracellular proteins. These events can trigger a signaling cascade that could ultimately alter gene expression, protein synthesis or cytoskeletal structure. We are studying these effects through collaborations in both numerical and experimental projects.
Development of new scaffold materials for vascularized engineered tissues
Another focus of our work is to develop and characterize a new hydrogel derived from self-assembling peptides that may be used for tissue engineering. These hydrogels are composed of short oligopeptides containing alternating sequences of hydrophobic and hydrophilic residues. These oligopeptides form beta strands that assemble into beta-pleated sheets and ultimately into a three-dimensional network. We are developing models that simulate the process by which the sheets assemble into networks of beta-sheet filaments that have a hydrophobic core. In addition, we are studying hydrogel monomers in solution to characterize the step-wise process by which they self-assemble into complex structures. These processes are particularly important in developing hydrogels for application in vascularized engineered tissues.
Professors Peter So, C. Forbes Dewey, Alan Grodzinsky, Matthew Lang, Douglas Lauffenburger, Linda Griffith, Frank Gertler
- Bathe, M. Shirai, A, Doerschuk, CM, Kamm, RD. Neutrophil transit times through pulmonary capillaries: The effects of capillary geometry and fMLP-stimulation. Biophys. J., 83:1917-1933, 2002.
- Younis HF, Kaazempur-Mofrad MR, Chung C, Chan RC, Kamm RD. Computational analysis of the effects of exercise on hemodynamics in the carotid bifurcation. Ann Biomed Eng, in press, 2003.
- Hwang W, Marini DM, Kamm RD, Zhang S. Supramolecular structure of helical ribbons self-assembled from a beta-sheet peptide. J Chem Phys, 118(1):389-397, 2003.
- Karcher H, Lammerding J, Huang H, Lee RT, Kamm RD, and Kaazempur-Mofrad R, A threedimensional viscoelastic model for cell deformation with experimental verification. Biophys J, 85(5): 3336-49, 2003.
- Hwang W, Zhang S, Kamm RD, and Karplus M. Kinetic control of dimer structure formation in amyloid fibrillogenesis. Proc Natl Acad Sci U S A 101: 12916-12921, 2004.
- Kaazempur-Mofrad MR, Isasi AG, Younis HF, Chan RC, Hinton DP, Sukhova G, LaMuraglia GM, Lee RT, and Kamm RD. Characterization of the atherosclerotic carotid bifurcation using MRI, finite element modeling, and histology. Ann Biomed Eng 32: 932-946, 2004.
- Zaman, MH, Kamm, RD, Matsudaira, P, Lauffenburger, DA. Computational model for cell migration in three dimensions. Biophys J 89: 1389-1397, 2005
- Yap B, Kamm RD. Mechanical deformation of neutrophils into narrow channels induces pseudopod projection and changes in biomechanical properties. J Appl Physiol 98(5):1930-9, 2005. Karcher H, Lee SE, Mofrad MRK, Kamm RD. A coarse-grained model for force-induced protein deformation and kinetics. Biophys J, in press.
- Park J, Kahng B, Kamm RD, Hwang W. Atomistic simulation approach to a continuum description of self-assembled &[beta]-sheet filaments, Biophys J, in press
Last Updated: April 8, 2008