Physical Principles of Membrane Signaling Reactions

Living cells calculate their logic through cascades of chemical reactions.  Although fundamentally stochastic, these molecular reactions are capable of executing signal transduction at a remarkable accuracy and efficiency.  A broad class of signaling reactions, such as those in T-cell receptor (TCR) triggering or receptor tyrosine kinase (RTK) signaling, takes place right at the plasma membrane.  This surface provides additional spatial, and chemical coordinates to allow “designs” of much more elaborate mechanisms to execute precise signaling, even in the presence of constant molecular noise.

My research focuses on understanding how these additional “degree of freedom” facilitate signal transduction of living systems.  I ask questions such as: what is the activation mechanism of membrane-associated proteins?  How is timing encoded by different molecular mechanisms (autoinhibition, dimerization, molecular assemblies, catalysis…etc.)?  How do these kinetic features help signaling accuracy (against molecular noise)?  What is the role of membranes?  Is there a general topology?  And finally, what is the design principle of early signal transduction in living cells?  Among these questions, I am constantly interested in the role of an individual molecule in ensemble signaling properties.

To have some hope in finding hints to these questions, I combine both experimental and modeling approach derived from the disciplines of physical chemistry, biochemistry, and cell biology.  In particular, quantitative single-molecule imaging techniques, membrane reconstitutions, and stochastic kinetic modeling are especially useful.  A few examples look like the following…

1

2_3

 

 

more coming soon…

 

 

 

Fig. 1 Protein assembly on membranes driven by multivalent protein-protein interaction
Fig. 2 Kinetic bifurcation in recruitment dynamics of cytosolic protein (yellow) driven by protein assembly

Selected References
Huang et. al., PNAS 2016, 113, 8218-8223.