Surface aggregation patterns of LDL receptors near coated pits II. The retrograde membrane flow-diffusion and generalized plaque-form insertion mechanism.

This study presents a theoretical exploration of the effects of mechanisms that, in addition to diffusion, may influence the surface dynamics and display of unbound receptors in the low-density lipoprotein (LDL) endocytic cycle in human fibroblasts. The factors considered here are a transverse membrane flow and a generalized plaque-form insertion mode. The proposed model permits estimations of aggregation rates of unbound receptors in coated pits as well as pictorial representations of their expected steady-state display on the cell surface. Our findings show that this display is determined in a fundamental way by the ratio of the strength of the flow to the diffusion coefficient. For measured values of the diffusion coefficient and the estimated value of the flow rate strength (and independent of the receptor insertion mode), the display predicted by our model is consistent with the capping phenomenon, i.e., a gradated clustering in the direction of flow streamlines. There could be suitable characterizations of the receptor reinsertion mode that would produce a substantial reduction in the mean capture time of LDL receptors by coated pits. In any event, our results show that the existence of a transverse membrane flow precludes the display of steady-state plaque-form surface clusters.