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Mechanobiology And Diseases Of Mechanotransduction


Donald E Ingber, MD, PhD 

From the Vascular Biology Program, Departments of Surgery and Pathology, Children's Hospital and Harvard Medical School

FROM ABSTRACT The current focus of medicine on molecular genetics ignores the physical basis of disease even though many of the problems that lead to pain and morbidity, and bring patients to the doctor's office, result from changes in tissue structure or mechanics. The main goal of this article is therefore to help integrate mechanics into our understanding of the molecular basis of disease. This article first reviews the key roles that physical forces, extracellular matrix and cell structure play in the control of normal development, as well as in the maintenance of tissue form and function. Recent insights into cellular mechanotransduction--the molecular mechanism by which cells sense and respond to mechanical stress--also are described. Reevaluation of human pathophysiology in this context reveals that a wide range of diseases included within virtually all fields of medicine and surgery share a common feature: their etiology or clinical presentation results from abnormal mechanotransduction. This process may be altered by changes in cell mechanics, variations in extracellular matrix structure, or by deregulation of the molecular mechanisms by which cells sense mechanical signals and convert them into a chemical or electrical response. Molecules that mediate mechanotransduction, including extracellular matrix molecules, transmembrane integrin receptors, cytoskeletal structures and associated signal transduction components, may therefore represent targets for therapeutic intervention in a variety of diseases.


The entire body is mechanically integrated through an extracellular matrix which attaches to cell membranes; cell membranes are attached to cell organelles through a filamentous cytoskeleton, including attachments to the nuclear membrane; the nuclear membrane is attached to the chromosomes through a nucleoskeleton. This is known as tensegrity or the Tensegrenous matrix.

Altered alignment in gravity or altered movement patterns (both are aspects of the subluxaion) adversely affect this tensegrenous matrix, altering the function of cell membranes, cellular organelles, and genetic expression.


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