Biophysical Society Thematic Meeting | Singapore

Mechanobiology of Disease

Wednesday Speaker Abstracts

Crawling Toward a Cure: Mechanobiology of Cell Migration and Differentiation in the Disease Microenvironment Krystyn J. Van Vliet 1,2 . 1 MIT Departments of Biological Engineering and Materials Science & Engineering, Cambridge, MA, USA, 2 Singapore-MIT Alliance for Research and Technology's BioSystems & Micromechanics, CREATE, Singapore. Several disease contexts include tissue microenvironments that differ substantially in mechanical and chemical properties as compared with healthy tissue. These microenvironment cues are shared among otherwise distinct diseases, ranging from tumors associated with soft-tissue cancers to brain lesions associated with multiple sclerosis and aging. Here, we will discuss how such mechanochemical stimuli affect key biophysical processes and biological responses at the cell-cell and cell-matrix interface. In the context of cancer, local gradients of acidity and stiffness extending from the tumor site can bias cell migration and promote recruitment of vasculature, initiated through changes in binding kinetics of extracellular matrix ligand-receptor. In the context of multiple sclerosis and aging, similar mechanochemical changes at brain lesions can directly affect proliferation and migration of glial stem cells, the differentiation of which is required to maintain or restore myelination of neural axons. We show how computational simulations from the molecular to cellular scale can be integrated with engineered materials and devices to mechanically probe and manipulate cell response, both for basic research of the disease states and for screening of therapeutics that target mechanotransductive pathways. Together, these biophysical mechanisms and engineering approaches provide increased understanding of and new perspectives to manage and treat such diseases.

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