Computational Model Provides Insight into the Distinct Responses of Neurons to Chemical and Topographical Cues

Abstract

Neuronal cell polarization (i.e., establishment of an axon) and axon guidance are mediated and controlled by mechanical and chemical signals from the environment. Unfortunately, an integrated approach to study cell–substrate interactions in a unified framework incorporating structural and chemical effects of the substrate has been lacking. In this paper, we present a new model combining experimental and computational methods to better understand the distinct behavior of E18 hippocampal neurons in response to topographical vs. immobilized chemical cues. We present results from our coarse-grain physiological computational model that correctly describes previously observed phenomena and predicts behavior that was subsequently tested through new experiments. The model differentiates topographical from chemical cues via a difference in cue spacing in these two substrates. Using the feature size spacing for topographical cues and a minimum step size, governed by the physics of filopodia protrusion, for chemical cues, the model successfully mimics the trend observed in experimental polarization probability for four different topographical feature sizes and constant chemical cue spacing. Our results not only show good agreement with experiments, but also provide novel suggestions for development of substrates for finer control of neuronal cell polarization.

Immobilized laminin concentration gradients on electrospun fiber scaffolds for controlled neurite outgrowth

“…Thus, the difference in the amount of protein was not large enough to produce an observable effect on neurite outgrowth. 51 In our research, the fiber diameters were 155 6 70 nm and thus much smaller than the feature size threshold identified in Forciniti's model. Most studies that have examined the effect of chemical and topographical cues have looked at their synergistic effect.…”

Controlling the kinetics of thiol-maleimide Michael-type addition gelation kinetics for the generation of homogenous poly(ethylene glycol) hydrogels

“…Topographical and mechanical cues are strong cellular activators that can override biochemical cues [8,9]. Thus, synthetic microenvironments aiming to generate extracellular matrix mimics must be able to control the topographical and mechanical cues throughout the material.…”

Actin–Fascin Bundle Formation Under Pressure

“…4 A number of studies have shown that topographical cues promote axogenesis, the formation of axon in neurons, and axon guidance, [6][7][8]14,19,28,27 which have been studied through both experimental and computational methods. 15 Many hypothesize that this cellular behavior is due to differences in tensile forces seen by the filopodia. These forces are seen by the migrating cell through the assembly and disassembly of focal contacts.…”