We are pleased to welcome Professor Dennis Discher
as our
2018-19 Distinguished Seminar speaker
March 15, 3:00 PM
106 Stanley Hall
Reception to follow
Mechanosensing:
from Scaling in ‘Omics & Nuclear Rupture to a Macrophage Checkpoint in Cancer
Dennis Discher
University of Pennsylvania
Dennis Discher, Ph.D., is the Robert D. Bent Professor of Chemical and Biomolecular Engineering, Bioengineering, and Mechanical Engineering and Applied Mechanics at the University of Pennsylvania, as well as Director of Penn’s Physical Sciences Oncology Center. He is a member of the National Academies of Medicine and Engineering, as well as a Fellow of the American Association for the Advancement of Science. Discher received his PhD from the UC Berkeley – UCSF Graduate Program in Bioengineering in 1993.
Abstract:
Scaling concepts have been successfully applied for decades in engineering and physics, including polymer physics, but applications to biology seem under-developed even though cells and tissues are built from polymers. Tissues such as brain and fat are very soft while tissues such as muscle and bone are stiff or even rigid – even when probed at the nanoscale, but relations to polymers and effects on cells are just now being uncovered. Having shown that matrix stiffness helps specify tissue lineages in vitro, we quantified protein levels in embryonic, mature, and cancerous tissues and also characterized cells on substrates of tuned stiffness. Extracellular collagen polymers directly determine tissue stiffness with near-classical scaling, and for embryonic heart, contractile beating of the organ and of isolated cells on synthetic gels is maximal when the stiffness is that of normal tissue, consistent with a ‘use it or lose it’ mechanism of tension-inhibited degradation. Cytoskeletal assembly likewise increases with stiffness and stresses the nucleus, which upregulates a nuclear structure protein called lamin-A (related to keratin in fingernails) that again scales with stiffness. Lamin-A assembly has evolved to tune nuclear stiffness and strength, and it varies widely between tissues and diseases including cancer. Recent studies relate to repair of DNA damage and to a macrophage checkpoint.
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