Effect of cell surface deformation on synaptic factor accumulation during the early stages of T cell activation

Abstract

Paracrine transfer of chemical factors between two interacting cells is a fundamental biological signaling process that can mediate cell differentiation, proliferation or even cell death. A hallmark geometrical feature of such interactions is deformation due to the flattening of membranes at the interface, referred to here as the synaptic gap. Of particular interest here is the accumulation of synaptic factor during the early stages of cell activation when one cell (REC) does not have sufficient surface receptors to absorb/adsorb the factor emitted by the other (EMC). Since factor accumulation has been conjectured to play an important role in cell activation, as in any reactive system, whether chemical or biological, an estimate of concentrations is essential for understanding the process. The purpose of this work is to provide just such an estimate by taking an engineering approach to this biological problem. In this regard, instead of providing a comprehensive “model” for paracrine delivery, the analysis is a solution of the quasi-steady diffusion equation in and around the interacting cells as a function of the degree of deformation and the kinetics of emission. Using a singularity method, it is found that, depending on the emission rate, cell deformation can lead to synaptic factor concentrations that are more than an order of magnitude higher than cells that retain a spherical shape. Analytical expressions for the radial variation of factor concentration within the gap are also derived. These analytical expressions, however, only provide the concentration difference between the synaptic axis and edge points but are nevertheless useful for estimating synaptic behavior and for validation of the computational method. The results also highlight the importance of deformation on paracrine signaling and indicate a mechanism by which cells can increase the range and function of transmitted factor by geometric alteration of the interface. While T cell activation is of primary interest, the analysis is cast in general terms so it can be applied to other non-absorbing RECs.