Analysis of Initial Cell Spreading Using Mechanistic Contact Formulations for a Deformable Cell Model

Adhesion governs to a large extent the mechanical interaction between a cell and its microenvironment. As initial cell spreading is purely adhesion driven, understanding this phenomenon leads to profound insight in both cell adhesion and cell-substrate interaction. It has been found that across a wide variety of cell types, initial spreading behavior universally follows the same power laws. The simplest cell type providing this scaling of the radius of the spreading area with time are modified red blood cells (RBCs), whose elastic responses are well characterized. Using a mechanistic description of the contact interaction between a cell and its substrate in combination with a deformable RBC model, we are now able to investigate in detail the mechanisms behind this universal power law. The presented model suggests that the initial slope of the spreading curve with time results from a purely geometrical effect facilitated mainly by dissipation upon contact. Later on, the spreading rate decreases due to increasing tension and dissipation in the cell's cortex as the cell spreads more and more. To reproduce this observed initial spreading, no irreversible deformations are required. Since the model created in this effort is extensible to more complex cell types and can cope with arbitrarily shaped, smooth mechanical microenvironments of the cells, it can be useful for a wide range of investigations where forces at the cell boundary play a decisive role.Author Summary: How cells spread on a newly encountered surface is an important issue, since it hints at how cells interact physically with the specific material in general. It has been shown before that many cell types have very similar early spreading behavior. This observation has been linked to the mechanical nature of the phenomenon, during which a cell cannot yet react by changing its structure and behavior. Understanding in detail how this passive spreading occurs, and what clues a cell may later respond to is the goal of this work. At the same time, the model we develop here should be very valuable for more complex situations of interacting cells, since it is able to reproduce the purely mechanical response in detail. We find that spreading is limited mainly by energy dissipation upon contact and later dissipation in the cell's cortex and that no irreversible deformation occurs during the spreading of red blood cells on an adhesive surface.