How Cells feel their environment: a focus on early dynamic events

Abstract

It is now well demonstrated that cell adhesion to a foreign surface strongly influences prominent functions such as survival, proliferation, differentiation, migration or mediator release. Thus, a current challenge of major practical and theoretical interest is to understand how cells process and integrate environmental cues to determine future behaviour. The purpose of this review is to summarize some pieces of information that might serve this task. Three sequential points are discussed. First, selected examples are presented to illustrate the influence of substratum chemistry, topography and mechanical properties on nearly all aspects of cell behaviour observed during the days following adhesion. Second, we review reported evidence that long term cell behaviour is highly dependent on the alterations of cell shape and cytoskeletal organization that are often initiated during the minutes to hours following adhesion. Third, we review recently obtained information on cell membrane roughness and dynamics, as well as kinetics and mechanics of molecular interactions. This knowledge is required to understand the influence of substratum structure on cell signaling during the first minute following contact, before the appearance of detectable structural changes. It is suggested that unraveling the earliest phenomena following cell-to-substratum encounter might provide a tractable way of better understanding subsequent events.

Figure 1. Studying the morphology of cell-to-substratum contact extension with interference reflection microscopy

Human T lymphocytes were deposited on glass surfaces coated with non-activating anti-HLA antibodies (A, C, E) or activating anti-CD3 antibodies (B, D, F). Cell morphology was monitored with standard microscopical observation (A, B) and interference reflection 15 minutes (C, D) or 30 minutes (E, F) after deposition. Clearly, contact extension was mediated by lamellipodia or filopodia depending of substratum structure. Bar length is 2 μm.

Figure 2. Three-dimensional reconstruction of cell surface morphology and dynamics near an adhesive surface

Human monocytic THP-1 cells were deposited on fibronectin-coated surfaces and observed with interference-reflection microscopy. The shape of the cell membrane is shown as a coded-colour map (A) or a 3-D drawing (B) together with the amplitude of spontaneous membrane fluctuations. Bar length is 2 μm. See ref for more details.