Membrane Biophysics


Overview 

Mechanisms of Membrane Fusion 
Membrane Properties 
Cell Signaling and Energy Transduction 
Membrane Biophysics Faculty 

Membrane biophysics is an important advanced training area within the Structural and Computational Biology and Biophysics (SCBB) program is Membrane Biophysics. Membranes are of fundamental importance for biological systems. They provide for cellular compartmentalization and control of the internal cell envrionment, they are sites for energy transduction and signaling, and many regulatory processes take place at membrane surfaces.                                                                                                                          
Training in Membrane Biophysics includes cutting edge research in several areas to address fundamental questions regarding:

 

 
  • Membrane protein structure and function
  • The mechanisms of membrane fusion
  • Membrane bilayer physical chemistry
  • Cell-signaling and Energy Transduction

      The Program offers an advanced course (PHY 813, Structure and Function of Biological Membranes ) to facilitate training in this area. The membrane biophysics faculty are internationally recognized, providing you with outstanding training in this exciting field

Structural Biology Research Areas at UVa

Membrane protein structure and function .

     Membranes and membrane proteins have become an important focus of the current efforts in structural genomics.  Membrane proteins represent a significant fraction of the proteins expressed by a cell (30 to 40%), yet less than one-half of one percent of the structures that have been deposited in the protein data bank are membrane proteins.  In addition, the majority of currently utilized pharmaceuticals target membrane proteins.

Several groups in the SCBB program  are examining the structure and molecular function of membrane proteins, utilizing novel spectroscopic or cryallographic approaches (Bushweller, Cafiso,Nakamoto,Perozo, Tamm and Wiener ).  These are some of the leading research groups in membrane proteins, and they have produced some of the most successful efforts in this area.  For example, research groups in this program were among the first to employ line narrowing TROSY techniques in combination with high-resolution NMR to generate structures for membrane porins.  Site-directed spin labeling (SDSL) is being employed

 

to characterize structural transitions that gate ion channels and drive active transport, yielding some of the first molecular models for function in these membrane protein systems.  Program researchers at the forefront of protein

crystallographic methods have also provided some of the first structures of membrane transporters.
 
In addition to investigating structures, a number of other groups are investigating the molecular function and regulation of membrane proteins such as ion channels, using molecular biology and advanced electrophysiological methods.  (These include the groups of  Moorman, Perozo, Perez-Reyes ).

 
Mechanisms of membrane fusion.
Mechanisms of membrane fusion.  Membrane fusion is a ubiquitous biological process that functions in the release of neurotransmitters, secretion and viral infection; yet, it remains one of the key unsolved problems in membrane biophysics and cell biology.  Membrane fusion is a highly regulated and directed process that appears to involve several classes of proteins. The protein components that coordinate and mediate fusion are not entirely characterized and the actual mechanisms by which twomembranes are brought into contact are not understood.		  


A number of research groups in the program are focused on cellular and biophysical aspects of fusion (Castle, Creutz, Tamm ) and are directed at understanding the protein components and/or membrane interactions that are necessary to facilitate and trigger fusion.  These groups are making leading contributions to understanding the membrane perturbations and protein interactions that promote fusion as well as the cellular machinery that directs fusion.

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Membrane properties. 
The properties of lipid bilayers play a key role in the behavior of membrane proteins and in the function of the cell.  Far from being a homogenous two-dimensional liquid, bilayers contain a wide range of lipid types that appear to segregate the membrane into specific domains or rafts.  These domains have been implicated in cell-signaling because they appear to play a role in the lateral organization of proteins that function in cell-signaling.  Lipid bilayers also solvate membrane proteins, and the physical properties (thickness, and curvature strain) can modulate membrane protein function.  Biological membranes typically contain a substantial fraction of negatively charged lipids, which results in an electrostatic membrane surface potential.   This electrostatic potential is exploited by cells to regulate that attachment of proteins that function in cell signaling pathways.  Several groups (Cafiso, Perozo, Tamm ) are exploring these physical properties of membranes and are providing new insight into how these properties regulate proteins, and control protein attachment.		  


 

Cell signaling and energy transduction.
A number of research groups are involved in investigations of cell-signaling and energy transduction (for example, the groups of Cafiso, Creutz, Holt, Moenter, Nakamoto ).  Cell-signaling encompasses a wide range of biochemical processes that control cell growth and metabolism in response to extracellular messengers.  Cell-signaling is a key NIH focus because it is central to cancer.  Many oncogenes (cancer producing genes) are in fact related to components of cell-signaling systems.

Many cell-signaling pathways are regulated by the attachment of water-soluble enzymes or regulatory proteins to the membrane interface, and membrane biophysics has made significant contributions understanding these processes.  For example, one ubiquitous Ca2+ regulatory motif is the

 
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C2 domain, which attaches to membranes in a Ca2+-dependent fashion.  SDSL has been used to determine the structures of C2 domains at the membrane interface, and has revealed the forces involved in regulating attachment.

Energy transduction process take place at and across membranes.  Several researchers in this program are investigating the process by which electrochemical  proton potentials are converted into ATP.

This process involves the action of a large membrane protein, which acts as a molecular motor.  A major challenge in this area is the synthesis and reconstitution of large membrane protein assemblies, and researchers in the membrane biophysics program are recognized as world leaders in this methodology.

For a list of faculty members conducting research in this area,  click here