Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2010.Cataloged from PDF version of thesis.Includes bibliographical references.Mechanical forces are critical to defining the physiological function of biological systems spanning length scales from 1 nm (single molecules) up to 1m (full mammalian systems). This work combines theoretical and experimental mechanics to gain insights into the physiological function of three biological systems at distinct length scales: collagen tissues comprised of wavy fibers (~ 1 mm), B lymphocyte membranes (~ 1 [mu]m), and amyloid protein fibers (~ 1 nm). The initial portion of this thesis addresses the mechanics of fibrous collagen tissues such as ligaments, tendons, and pericardium that serve as load bearing components in biological systems. A novel micromechanical model describing the force-extension of wavy fibers comprising these tissues is integrated with bundle and network frameworks. The developed models accurately predict the mechanical behavior of bundled fiber tissues (i.e ligaments and tendon) and fibrous membranes (i.e. vessel walls and pericardium) and elucidate deformation mechanisms within these tissues. Moving down in length scale, the second part of this thesis employs single cell experiments with optical tweezers to characterize the mechanical behavior of the B cell membrane, which is a critical component of its physiological functions including migration and antigen detection. Our results show that the mechanical properties of the membrane, specifically the effective viscosity of the membrane, evolve upon activation of B cell biochemical machinery. We further identify the presence of receptors in membrane nanotubes conferring B cells with the ability to sense antigen at remote locations. Lastly, this thesis studies the aggregation and underlying structure of amyloid forming proteins by characterizing their physical properties at the fibril and single molecule level. Amyloid formation, which is associated with many diseases including Alzheimer's, results from the aggregation of misfolded proteins. This work combines optical trapping with fluorescence imaging to quantify the physical properties and molecular interactions of amyloid fibers formed from polymorphic variants of the yeast prion protein, Sup35. Our results show that Sup35 polymorphism leads to distinct physical properties of amyloid aggregates. We further subject fibers to unfolding and rupture to elucidate structural details of misfolded Sup35.by Carlos E. Castro.Ph.D
