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Their Mechanical Journey from Birth to Turn-over or Maturation

Materials Science and Engineering Seminar

Sangyoon J. Han, Ph.D.
Department of Biomedical Engineering
Michigan Technological University

Abstract: When adherent cells attach to their physical environment, not an entire cell membrane engages with the ligands in the extracellular matrix. Only a fraction of the cell membrane, with a specific receptor has turned out to form a punctate structure, referred to as “focal adhesions”. Focal adhesions connect the extracellular matrix to cytoskeleton inside a cell and transmit mechanical forces generated by the cytoskeleton toward the ECM. At the same time, interestingly, they have been found to be able to transduce the force they “felt” into biochemical signals, which triggers cellular responses that lead to changes in a wide variety of cell functions including cell proliferation and differentiation. In this talk, general structure and function of focal adhesions will be briefly discussed. However, majority of the time will be dedicated to what is happening when these focal adhesions are just born, whether these nascent adhesions are able to transmit forces and how these forces are related with adhesions maturation and turn-over. To study this, 1) a tool to resolve small force from tiny adhesions and 2) a framework that allows linking mechanical force to highly heterogeneous molecular events are required. In this talk, how these two issues are addressed computationally will be discussed. The key assay we have developed to address these issues is Traction Force Microscopy (TFM), which involves continuum mechanics and sparsity regularization of the inverse problem solution. The measurements from the tool and the framework suggest evidence of mechano-sensitivity of a significant subset of nascent adhesions and highlight differential roles of adhesion molecules in mechano-transmission.

Bio: Sangyoon Han received his Ph.D. with Dr. Nathan Sniadecki from Mechanical Engineering at University of Washington (UW) in 2012 and performed postdoctoral training with Dr. Gaudenz Danuser in the Department of Cell Biology at Harvard Medical School and University of Texas Southwestern Medical Center from 2012 to 2017. Before his Ph.D., he received B.S and M.S. degree from Mechanical Engineering at Seoul National University, Seoul, Korea in 2002 and 2004. He joined Michigan Tech, Biomedical Engineering from the fall 2017. His lab is interested in understanding the dynamic nature in force modulation occurring across cell adhesions and cytoskeleton that regulates molecular sensing and downstream signaling response. His lab develops a minimally-perturbing experimental approach that uses live-cell microscopy and computational software that processes the microscopic images to reveal linkages among mechanical forces, heterogeneous adhesion morphodynamics and cell migration. Traction Force Microscopy Package (TFM Package) is one software released to, and widely used by, mechanobiology community.