Mechanical Modulation of Stem Cell Shape and Fate

Case Western Reserve University, Cleveland OH

Investigators

Abstract

This study investigates the role of cell mechanics on enforcement of cell shape and cell fate (cell lineage commitment) during de novo formation of tissues. Shape and fate are intrinsic manifestations of form and function at the cellular level. At the length scale of the tissue, mechanical stress influences structure and function during prenatal development and postnatal healing. At the length scale of the embryonic mesenchymal stem cell, recent data demonstrate a high degree of mechanosensitivity, which modulates their assembly to form tissues and organs. Furthermore, recent developmental biology and cell mechanics studies implicate cell shape as a powerful modulator of cell fate after homing of stem cells to target tissues in adult organisms. One aim of this research program is to study shape as a measure of a cell's adaptation to prevailing mechanical stimuli during de novo tissue formation. A further aim is to correlate the spatiotemporal enforcement of shape, via mechanical signals, to the specification of cell lineage (fate). Finally, a third goal is to test the feasibility of exploiting mechanical cues to engineer templates of bone and blood vessels for tissue replacements. The research program will help to decipher how mechanical signals, intrinsic to life on Earth, modulate the adaptation and specialization of cells to their environment during prenatal development as well as engineering and manufacture of tissues. Through elucidation of Nature's mechanobiological engineering paradigms, mechanical cues can be exploited to prevent defects during development as well as to generate tissues in the laboratory and in the surgical operating room. The impact of the research program on education will be amplified through tight integration of the research approach and insights with a newly developed college level course Cell and Tissue Engineering: Learning from Nature's Mechanobiological Paradigms? and a Science, Technology, Engineering and Math (STEM) high school class which will be taught to student groups from Cleveland Municipal School District and inner ring schools.