This project involves a new computational methodology developed to address a fundamental challenge in the computer simulation of complex biomolecular systems: the interfacing and feedback between multiple spatial and temporal scales. Biomolecular systems can possess dynamics that occur on time scales ranging from the microscopic (nanoseconds) to the macroscopic (milliseconds to hours), and on length scales from Angstroms to millimeters and beyond. The specific goal of the project will be to simulate such processes in lipid bilayers (cell membranes). The focus will therefore be on the development and application of the new simulation technology to explore the nonlinear response of biomembranes to external perturbations such as mechanical stresses, pH gradients, osmotic forces, etc. The research will utilize an integrated computer simulation capability to link the microscopic, atomic level simulation information with macro-scale, continuum-level modeling. Viewed in its broadest context, this interdisciplinary project represents a step toward the eventual simulation of the key components of living organisms beginning with atomistic simulation information at its foundation. In the shorter term, the capability to model the response of a cell membrane to various environmental perturbations opens a pathway to design agents to modulate the properties of cell membranes in other contexts; for example, to increase/decrease susceptibility to lysis, to modulate permeability of specific bilayers in order to increase drug transport and to help design novel liposomes for drug delivery purposes.