Membrane Biophysics | Theory and Experiment

Date :From 2012-05-07 To 2012-06-01
Advisory committee :
Local coordinators :Zhong-can Ou-Yang(Co-Chair), Zhanchun Tu(Contact Person), Yajun Yin, Pingwen Zhang(Co-Chair)
International coordinators :Tobias Baumgart, Sovan Das(Contact Person), Markus Deserno, Qiang Du(Co-Chair), Reinhard Lipowsky(Co-Chair)
Bio-membranes are very crucial for the life of cells. These self-assembled, quasi-two-dimensional structures not only isolate a cell from its surroundings, but also compartmentalize the interior of eucaryotic cells into a variety of distinct organelles (such as the nucleus, the endoplasmic reticulum, or the Golgi apparatus). In conjunction with various membrane-bound proteins bilayer membranes frequently assist fundamental cell biological functions, such as sorting and transport of lipids and proteins, signaling, endocytosis, adhesion, etc. Consequently, it is very important to quantitatively understand their mechanical and physicochemical behavior. Besides gaining fundamental scientific insight, a detailed knowledge of lipid bilayer membranes will also advance biotechnology applications, such as drug delivery and targeted therapies.

This four-week program will cover the following areas: 

(i)    Experimental investigations of lipid vesicles and cell membranes:
Experimental research in the past few decades on both living cells and a variety of idealized model membranes has revealed a great deal about the structure and function of cellular membranes. For instance, model membranes in the form of mixed lipid bilayer vesicles featuring a fluid-ordered (lo) and fluid-disordered (ld) phase coexistence have been very carefully analyzed over a range of temperatures. Given a suitably chosen lipid composition, these systems can represent certain aspects of real biological cell membranes very well, and this permits highly accurate and controlled studies of how key biological processes (such as signaling between proteins, sorting and transport of proteins, endocytosis, and adhesion) are influenced by the presence and extent of a fluid-phase coexistence. Furthermore, the recent spectacular advances in optical microscopy enable us to directly examine living cells at very high resolution and refine our understanding of membranes physiology in vivo. Extensive research is currently being pursued to explore the mechanisms that determine the laterally heterogeneous structure of the plasma membrane, membrane-protein interactions, and the dynamic sorting of lipids and proteins that takes place within the Golgi apparatus. While this research is predominantly aimed at understanding cell membrane functionality, it also complements and critically informs the development of theory and computational tools. Accordingly, we propose a detailed discussion of recent advances in experimental methods involving lipid bilayer membranes in our program.

(ii)    Theory and modeling of lipid bilayer membranes:
The elastic and thermodynamic bilayer properties, such as its bending stiffness and spontaneous curvature, or the line tension between two coexisting phases, are of considerable importance for macroscopic membrane behavior. For instance, the spontaneous curvature co-determines the preferred configuration of a piece of unconstrained membrane without any force or moment acting on it, and the line tension along a liquid-liquid phase boundary gives rise to nontrivial stresses and moments that not only affect the membrane shape but also the location of the line itself. All these membrane-related quantities, together with the osmotic pressure across the membrane or other external forces (due for instance to adhesion or attachment to filaments) determine the equilibrium shape of a vesicle and co-determine the statics and dynamics of vesiculation and fission (closely related to endo- and exocytosis or viral budding), adhesion (important for instance in sensing and locomotion), or mediated interactions (relevant for instance in signaling). The influence of the physical parameters mentioned above are often investigated by studying the equilibrium shapes of fluid membranes, determined on the basis of a very well characterized and enormously successful continuum model resting on curvature elasticity. This section of our program will focus on various extensions and refinements of the mechanical models proposed for the study of lipid membranes. Specific topics include the efficient modeling of elasticity, phase separation, thermal shape fluctuations, and adhesion of vesicles to substrates. The role played by the additional cytoskeleton in cell membranes will also be explored.

(iii)    Computational investigations of lipid bilayer membranes:
Along with experimental and theoretical studies, computation has gained an increasingly more important role in the advancement of lipid membrane research. Computational tools such as molecular dynamics simulations, Monte Carlo, phase field methods, immersed boundary techniques, etc. have enabled researchers to answer many fundamental questions that are difficult to address directly in experiment or too complex to permit an analytic treatment. Computational tools such as molecular dynamics simulations approach the problem from the point of view that membranes are composed of molecules that are interacting with each other. In contrast, tools such as the phase field or immersed boundary method aim to find approximate solutions to the macroscopic shape equations obtained from continuum theory. Self assembly of lipid molecules into a membrane, membrane protein interactions, budding and fission, virus entry or exit and nano-particle uptake by membranes, dynamics of lipid vesicles/cells in viscous fluid, adhesion of multicomponent membranes and of membranes to substrates of complex geometry are just a few examples for which these techniques have been applied with great success. In this part of our program we would like to discuss recent advances and new challenges in this field.

The rough schedule of this program is:
(a) May 7, Opening.
(b) May 7 – 9, Tutorial lectures on lipid membranes, experimental techniques.
(c) May 8 – 15, Workshop on fundamentals of lipid membrane and experimental research. (6-8 lectures/day)
(d) May 16–June 1, Theoretical modeling, computational simulation and experimental investigation on membranes. (2 lectures/day; discussion and collaboration between participants)

Remark: We suggest the short-term participants arrange your schedules to cover the workshop from May 8 to May 15 at least.