Woodruff School of Mechanical Engineering
Models of Cellular Mechanobiology, from Focal Adhesions to Nuclear Pores
Prof. Mohammad R. K. Mofrad
University of California Berkeley
Wednesday, January 16, 2013 at 11:00:00 AM
MRDC Building, Room 4211
Cells sense mechanical signals and actively respond by altering their phenotype. Cellular mechanotransduction is mediated by a combination of biochemical and biophysical mechanisms via mechanically induced changes in the structure and function of specific molecules. These mechanosensing molecules can function to initiate key biological processes, e.g. focal adhesion formation at the interface of cell’s interaction with the extracellular matrix. Another example of potential molecular systems likely taking part in regulation of mechanotransduction is the nuclear pore complex that controls the nucleocytoplasmic traffic, regulating gene expression and protein synthesis. In this talk, I will present some of our recent efforts aimed at better understanding of the molecular players in cellular mechanotransduction, focused on two particular molecular machineries, namely the focal adhesions and the nuclear pores. A series of molecular dynamics investigations will be presented to explore the potential mechanosensing and mechanotransduction functions of key molecules involved in focal adhesion formation. Using state-of-the-art molecular dynamics modeling and simulation techniques, the molecular mechanics of these proteins, their force-induced activation, and changes in their molecular conformation and binding partnership will be discussed. I will also present our new “biological breadboard” platform for programmable, addressable adhesion/detachment of the cell to gold surfaces modified with a thiol-functionalized RGD peptide. Finally, I will present our recent models to explore the exquisite function of the nuclear pores and the relationship between biochemical factors and mechanical behavior of cargo being transported across the nuclear pore.
Biography: Dr. Mohammad R. K. Mofrad is currently associate professor of Bioengineering and Mechanical Engineering at the University of California Berkeley, where he is the director of Molecular Cell Biomechanics Laboratory (http://biomechanics.berkeley.edu) and also a faculty scientist with Lawrence Berkeley National Lab. Dr. Mofrad received his B.A.Sc. degree from Sharif University of Technology in Tehran, Iran, before moving to Canada where he received his M.A.Sc. and Ph.D. degrees from the Universities of Waterloo and Toronto, respectively. After post-doctoral work at MIT and Harvard Medical School, he joined the faculty at Berkeley. Dr. Mofrad is interested in the areas of Molecular Cell Biomechanics and Mechanotransduction, and Cardiovascular Disease. Mofrad Lab's research program encompasses the development of molecular and multiscale models of cell mechanobiology, with specific attention to the role of two macromolecular systems, namely the nuclear pore complex and integrin-mediated focal adhesions. Focal adhesions are the immediate sites of cell's interaction with the extracellular microenvironment, and as such they play a key role in mechanosensing and mechanotransduction at the interface of the cell with the extracellular world. Nuclear pores exquisitely control the traffic in and out of the nucleus, thereby regulating the gene expression and protein synthesis. Prof. Mofrad has authored and co-authored more than 80 peer-reviewed papers in varied journals ranging from Biophysical Journal, Journal of Biomechanics and PLoS Computational Biology to Journal of MEMS, Biomaterials and Lab on a Chip. He has also co-edited three books titled Cytoskeletal Mechanics: Models and Measurements, Cellular Mechanotransduction: Diverse Perspectives from Molecules to Tissue (published by Cambridge University Press) and Computational Modeling in Biomechanics (published by Springer).