"Engineering Cells and Microsystems to Study Mechanobiology" 

Beth L. Pruitt, Ph.D. *

Associate Professor

Silas H. Palmer Faculty Scholar, Departments of Mechanical Engineering and Bioengineering and Molecular and Cellular Physiology

Stanford University

ABSTRACT

Living organisms generate and respond to mechanical forces and these forces are sensed and created by specialized cells in the body. Force generation and sensing, or more broadly the mechanobiology coupling tissue (cell) mechanics and biology, are essential in normal development, wound healing, and tissue homeostasis. Our mechanical senses of hearing and touch allow us to navigate our environment and interact with one another, yet they remain the least understood of our perceptive senses. Basic life sustaining functions such as breathing, circulation, and digestion are driven autonomously by coordinated contraction of specialized muscle cells, yet how these functions incorporate active feedback via force sensing at the cellular level is an area of active study.  Meanwhile, a variety of specialized stretch activated receptors and mechanically mediated biochemical signaling pathways have been identified in recent years. Importantly, defects in proteins of these mechanically mediated pathways and receptors have been implicated in disease states spanning cardiovascular disease, cancer growth and metastasis, neuropathy, and deafness. Thus, understanding the mechanical basis of homeostasis (health) and defective cell renewal function (disease) increasingly requires us to consider the role of mechanics. To study how cells and tissues integrate mechanical signals, we and others have developed specialized cell cultures systems and micromachined tools to stimulate and measure forces and displacements at the scale of proteins and cells. A key feature of such experiments is the ability to observe cell outputs such as morphological changes, protein expression, electrophysiological signaling, force generation and transcriptional activity in response to mechanical stimuli.