Development of a model to explain the effect of variable membrane compliance on single molecule adhesive bond force

Thesis (S.B.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2004.Includes bibliographical references (leaves 28-30).The intermolecular bond force existing between adhesive membrane receptors and extracellular matrix (ECM) molecules is believed to regulate key cell functions, such as growth, apoptosis, motility, and mechanotransduction. From a clinical perspective, understanding the mechanics of cell-matrix bonds may be key to unraveling the factors, which promote or inhibit wound healing as well understanding the mechanisms by which cancer cells grow and metastasize. Models describing molecular bond behavior have been studied for close to a century, but accumulation of knowledge in this area has accelerated in recent years due to the advent of methods, such as atomic force microscopy, to study biological forces in the piconewton range. Based on the work of Evans and others, the concept has emerged that molecular pairs do not possess characteristic bond strength, but rather that bond strength varies as a function of the rate at which a disrupting force is applied. On a theoretical basis, this effect may be explained by the complexity of the energy landscape typical of most biological bonds. Thus, bonds subjected to a lower rate of force loading exhibit weaker bond force, owing to the added contribution of thermal activation energy, while bonds subjected to a higher rate of force loading exhibit higher bond force. What is not generally considered is the way in which membrane compliance in cells may contribute to perceived force loading, and in turn, bond force. Our laboratory has previously determined a relationship between membrane compliance and bond force employing high-resolution force spectroscopy, whereby the more deformable domains of the cell membrane are associated with lower bond force and the less deformable domains(cont.) are associated with higher bond force. The purpose of this thesis is to analyze this distinction in light of Evans' theory of bond energetics, and to develop a model accounting for the contribution of membrane mechanics to single bond force.by Brendan T. Maddigan.S.B