Biomechanics: cell research and applications for the next decade

Abstract

With the recent revolution in Molecular Biology and the deciphering of the Human Genome, understanding of the building blocks that comprise living systems has advanced rapidly. We have yet to understand, however, how the physical forces that animate life affect the synthesis, folding, assembly, and function of these molecular building blocks. We are equally uncertain as to how these building blocks interact dynamically to create coupled regulatory networks from which integrative biological behaviors emerge. Here we review recent advances in the field of biomechanics at the cellular and molecular levels, and set forth challenges confronting the field. Living systems work and move as multi-molecular collectives, and in order to understand key aspects of health and disease we must first be able to explain how physical forces and mechanical structures contribute to the active material properties of living cells and tissues, as well as how these forces impact information processing and cellular decision making. Such insights will no doubt inform basic biology and rational engineering of effective new approaches to clinical therapy.

Fig. 1

Distribution of normalized fluid stresses acting on the membrane of a migrating leukocyte with active cytoplasmic projections (pseudopods). The cell is attached to a flat glass surface and exposed to a constant shear stress. The fluid shear stress was determined by solution of the equation of motion for a Newtonian fluid (plasma) with non-slip condition on the cell membrane and on the substrate. All stress values are normalized by the applied shear stress (2.2 dyn/cm²) on the cell substrate away from the cell. The cell shape was reconstructed from a three-dimensional stack of confocal images with a fluorescent membrane label. Su, SS: Fluid Stress on the Surface of a Migrating Leukocyte in a Flow Field and the Involvement of Formyl Peptide Receptor in Its Mechanotransduction. Ph.D. Thesis. Department of Bioengineering, University of California San Diego, 2007.

Fig. 2

Traction microscopy image: Traction stress field exerted by a rat pulmonary microvascular endothelial cell upon its substrate. Inset: Phase contrast image at reduced magnification. Scale: Shear stress in Pascals. Adapted from

Fig. 3

In vitro flow assays yield images obtained from both top-view and side-view of an adherent cell under flow conditions compared with in vivo images. ,