@article{monine_haugh_2008, title={Signal transduction at point-blank range: Analysis of a spatial coupling mechanism for pathway crosstalk}, volume={95}, ISSN={["0006-3495"]}, DOI={10.1529/biophysj.108.128892}, abstractNote={The plasma membrane provides a physical platform for the orchestration of molecular interactions and biochemical conversions involved in the early stages of receptor-mediated signal transduction in living cells. In that context, we introduce here the concept of spatial coupling, wherein simultaneous recruitment of different enzymes to the same receptor scaffold facilitates crosstalk between different signaling pathways through the local release and capture of activated signaling molecules. To study the spatiotemporal dynamics of this mechanism, we have developed a Brownian dynamics modeling approach and applied it to the receptor-mediated activation of Ras and the cooperative recruitment of phosphoinositide 3-kinase (PI3K) by activated receptors and Ras. Various analyses of the model simulations show that cooperative assembly of multimolecular complexes nucleated by activated receptors is facilitated by the local release and capture of membrane-anchored signaling molecules (such as active Ras) from/by receptor-bound signaling proteins. In the case of Ras/PI3K crosstalk, the model predicts that PI3K is more likely to be recruited by activated receptors bound or recently visited by the enzyme that activates Ras. By this mechanism, receptor-bound PI3K is stabilized through short-range, diffusion-controlled capture of active Ras and Ras/PI3K complexes released from the receptor complex. We contend that this mechanism is a means by which signaling pathways are propagated and spatially coordinated for efficient crosstalk between them.}, number={5}, journal={BIOPHYSICAL JOURNAL}, publisher={Elsevier BV}, author={Monine, Michael I. and Haugh, Jason M.}, year={2008}, month={Sep}, pages={2172–2182} } @article{berezhkovskii_monine_muratov_shvartsman_2006, title={Homogenization of boundary conditions for surfaces with regular arrays of traps}, volume={124}, number={3}, journal={Journal of Chemical Physics}, author={Berezhkovskii, A. M. and Monine, M. I. and Muratov, C. B. and Shvartsman, S. Y.}, year={2006} } @article{monine_haugh_2005, title={Reactions on cell membranes: Comparison of continuum theory and Brownian dynamics simulations}, volume={123}, ISSN={["1089-7690"]}, DOI={10.1063/1.2000236}, abstractNote={Biochemical transduction of signals received by living cells typically involves molecular interactions and enzyme-mediated reactions at the cell membrane, a problem that is analogous to reacting species on a catalyst surface or interface. We have developed an efficient Brownian dynamics algorithm that is especially suited for such systems and have compared the simulation results with various continuum theories through prediction of effective enzymatic rate constant values. We specifically consider reaction versus diffusion limitation, the effect of increasing enzyme density, and the spontaneous membrane association/dissociation of enzyme molecules. In all cases, we find the theory and simulations to be in quantitative agreement. This algorithm may be readily adapted for the stochastic simulation of more complex cell signaling systems.}, number={7}, journal={JOURNAL OF CHEMICAL PHYSICS}, publisher={AIP Publishing}, author={Monine, MI and Haugh, JM}, year={2005}, month={Aug} }