Introduction
Lipid bilayer membranes play a central role in living systems: all cells are encapsulated by membranes; membranes divide the eukaryotic cell into compartments to sequester specific cellular functions; membranes are the sites where many cellular machineries carry out their tasks. Since living cells function out-of-equilibrium and are constantly subjected to stresses (e.g. cells in the blood flow), the non-equilibrium behavior of membranes is emerging as an important research area at the forefront of biophysics research.
The interplay of electric potential and morphology of biomembranes
An electric potential difference across the plasma membrane is common to all living cells and is crucial for the generation of action potentials for cell-to-cell communication. Beyond excitable nerve and muscle, bioelectric signals conjugated with the transmembrane potential control many cell behaviors such as migration, orientation, and proliferation, which play crucial role in embryogenesis, would healing, and cancer progression. The mechanisms of cellular responses to electric stimuli are largely unknown. An electricity-centered view, epitomized by the Hodgkin-Huxley model, focuses on the voltage-dependent ion channels. However, in recent years membrane mechanics is emerging as a potentially important player: membrane deformations are detected to co-propagate with action potentials, several ion channels have been found to be both voltage-gated and mechanosensitive, and lipid rafts have been implicated as electrosensors. Assessment of the relevance of these membrane-related effects in bioelectric phenomena requires fundamental understanding of the coupling between membrane morphology, stresses, and voltage, which is limited.
This research aims to determine how membrane electric potential elicits membrane responses such a stretching or compression, curvature, and phase transitions, and vice versa, how changes in the membrane morphology modulate the transmembrane potential.
The mathematical modeling involves free boundary problems exhibiting complex dynamics. My group uses continuum theory to model the ions transport, motion of a charged lipid membrane interface and the surrounding liquids. A collaboration with Prof. Monica Olvera de la Cruz seeks to develop molecular dynamics simulations, capable of resolving large (microsecond and micrometer) scales, considering polarization, dielectric variations, and the ionic environment, to illuminate the molecular mechanisms of voltage-membrane morphology coupling and guide the development of continuum models of membrane flow in the presence of electric fields.
Experimentally, using giant unilamellar vesicles (GUVs) as a model membrane system we develop novel methodologies to probe the dynamic coupling between shape and voltage of biomembranes. The techniques are based on the flickering spectroscopy (analysis of the thermally driven micron- and sub-micron membrane undulations) and GUV deformation in applied electric fields. We investigate membranes with broad range of compositions mimicking biological membranes. The experimental results inform the mathematical models in terms of relevant physics and material parameters, and vice versa, the theories provide guidance for the experiments.