Stochastic models of cotransport

Cell membrane transport plays a pivotal role in facilitating communication between the cell and its environment. Within this context, cotransport emerges as a vital mechanism, harnessing electrochemical gradients to energize the transmembrane translocation of solutes. The aim of my doctoral research is to improve the theoretical understanding of cotransport along two axes. First, by developing models consistent with the experimental data, and second, by using these models to provide experimentally testable predictions on the cotransport kinetics. To achieve this aim, we obtained a series of results that can be categorized into two main groups: general results, which have implications for the general theory of cotransport and apply to any transporter, and specific results, which are applicable to particular cotransporters. Within the general results category, we have found strong evidence to support the thesis that cotransporters exhibit enzyme-like behavior, shedding light on the debate regarding whether secondary active transport can be described using the theoretical framework of enzymology. Within the specific results category, we investigated the dynamics of three cotransporters, namely, the lactose permease of E. coli, LacY, the sodium-glucose transporter of type 2, SGLT2, and the sodium-aspartate symporter from Pyrococcus horikoshii, GltPh. The present thesis leaves a valuable legacy by providing insightful contributions to the general theory of cotransport, as well as presenting models that can be helpful in simulating uptake assays of some specific cotransporters.