Membrane fluidity: Both fundamental and functional

The membranes which enclose our cells are very thin sheets — not solid like a balloon, but rather fluid, like a soap film. Embedded in the membrane are a plethora of molecules that conduct the chemical conversation between the cell and the world outside. This chemical conversation (or “signaling”) underlies both normal functions, like exchange of neurotransmitters in the brain, and abnormal ones, like cancer growth and progression.

But what choreographs signaling, so that partners find each other at the appropriate place and time? A crucial part of the answer is the viscosity of the membrane — Is it thick like honey, or thin like water? Measuring the viscosity of a cell membrane in an experiment is extremely challenging, and interpretation of the results relies on difficult to test assumptions.

This project will therefore combine several different experimental measurements with detailed simulations of membranes. The simulations (which utilize federally funded supercomputers) are designed to fill in the gaps in the experiments, so that together they provide a complete understanding of the chemical origins of membrane viscosity. Through a collaboration with the Delaware Teachers Institute the research team will develop a series of lessons on the biophysics of fluids, which will be disseminated to twelve Delaware high school teachers.

This content will both enrich the curricula of high schools throughout the state, and also expose students to the field of biophysics as a possible course of study for students who are strong in math, but also excited by developments in biology and health sciences.

Cells actively regulate the fluidity of their membranes in response to changes in external conditions, like temperature, salinity, or pressure. Sinensky discovered this “homeoviscous adaptation” in the 1970’s, in bacteria that were grown at different temperatures, yet maintained constant fluidity. Despite the fundamental importance of membrane fluidity, it is still not understood how it emerges from the complex milieu of the cell membrane.

Indeed, experimental measurements differ in their reports of membrane viscosity by more than a factor of ten, depending on the technique and how the measurement is interpreted. This knowledge gap will be filled by a combination of detailed simulations of membranes and several types of experiments. The simulations will use the most accurate and detailed models for membranes and will leverage federally funded supercomputing platforms.

The experiments cover length and timescales from picoseconds to microseconds, and will use federally funded beamlines (neutron scattering at the National Institute of Standards and Technology and x-ray scattering Brookhaven National Lab). By integrating the simulations and experiments the investigators will resolve discrepancies in existing measurements and identify what factors determine membrane viscosity.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.