This event is occurring at a different time and place than the other BME seminars in the series. Please note that Alex Cartagena-Rivera will be speaking on Wednesday, February 14 at 3:30 pm in LBME 1123.


Alexander X. Cartagena-Rivera
BME Faculty Candidate and Guest Speaker
National Institute on Deafness and Other Communication Disorders
National Institutes of Health

“Cellular and Tissue Mechanical Regulation – Towards an Understanding of Self-Organization in Mechanobiology”

Abstract:
Determination of critical physical parameters of complex biological systems is key for understanding the relationships between molecular structure, biophysical properties, and biological function of cells and tissues. Recently, I developed novel minimally invasive atomic force microscopy (AFM) methods for the quantitative determination of relevant mechanical properties of the (i) actomyosin cortex of nonadherent cells, (ii) apical surface and apico-lateral junctional complexes of polarized epithelia, and (iii) sensory stereociliary bundles in the inner ear.

The cortical actin cytoskeleton lies just beneath the plasma membrane defining cell shape and mechanical properties, and thus plays a key role in cellular processes such as migration and morphogenesis, and contributes to the macroscale mechanics of tissues. I developed an AFM method for using an AFM with tipless cantilevers to determine actomyosin cortical tension, elastic modulus, and intracellular pressure of human fibroblast and melanoma nonadherent cells. I applied this new method to determine changes in cortical actin molecular dynamics after treatment with drugs and administration of siRNAs targeting the actomyosin cytoskeleton. The results suggested that myosin II activity, actin polymerization, and actin branching all contribute to cortex tension and intracellular pressure, whereas the cortical elastic modulus is more dependent on myosin II activity. Subsequently, I developed a novel noncontact AFM method to measure the apical surface tension, fluidity, and intercellular adhesive forces in polarized epithelia. This study demonstrated dramatic changes in epithelial mechanics of the adherent junctional complex after depletion of the tight junction proteins zonula occludens 1 and 2. Lastly, I extended the noncontact AFM method to determine the elastic stiffness and viscous damping of stereocilia bundles in the inner ear sensory cells. The results suggested that deletion of the horizontal top connectors in the outer hair cells dramatically reduces the bundle mechanics, which correlates with other studies showing that absence of top connectors eliminates bundle cohesion and the waveform distortion products.
Altogether, these novel noninvasive AFM methods, designed to measure cell and monolayer mechanical properties are easily and generally applicable to a large variety of cell based experiments and should dramatically improve our understanding of how changes in mechanical properties are associated with critical cellular processes, development, and disease progression.