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 remarkable accuracy and efficiency. A broad class of signaling reactions takes place right at the plasma membrane, such as the receptor tyrosine kinase (RTK) signaling and immune cell signaling. Cell membranes provide additional spatial and chemical coordinates to allow “designs” of much more elaborate mechanisms to carry out robust signaling.
My research focuses on understanding how these additional “degrees of freedom” facilitate signal transduction of living systems. We pursue this quest by first resolving the molecular mechanisms of signaling reactions, at the ensemble and single-molecule levels. With sufficient determination of how these reactions occur, we may be able to then extract general principles that govern cellular signaling.
My approach combines experimental and modeling methods derived from physical chemistry, systems biology, biochemistry, and cell biology. In particular, we make use of membrane reconstitution to map complex signaling reactions into quantifiable systems. This strategy naturally integrates physical methods, including advanced imaging techniques and stochastic kinetic modeling, to resolve signaling processes. A few examples look like the following:
Movie 1 Reconstituted protein condensates on membranes
Movie 2 Kinetic bifurcation of recruitment dynamics (yellow) driven by condensates
Movie 3 Single-molecule activation assay on supported membranes. The microarray allows the unambiguous assignment of enzymatic turnover (red) to a single recruitment event (yellow).
Selected References
Huang et. al., PNAS 2016, 113:8218-8223.
Huang et. al., Science 2019, 363:1098-1103.