Abstract

Topography of the extracellular environment is now recognized as a major biophysical regulator of cell behavior and function. The study of the influence of patterned substrates on cells, named contact guidance, has greatly benefited from the development of micro and nano-fabrication techniques, allowing the emergence of increasingly diverse and elaborate engineered platforms. The purpose of this review is to provide a comprehensive view of the process of contact guidance from cellular to subcellular scales. We first classify and illustrate the large diversity of topographies reported in the literature by focusing on generic cellular responses to diverse topographical cues. Subsequently, and in a complementary fashion, we adopt the opposite approach and highlight cell type-specific responses to classically used topographies (arrays of pillars or grooves). Finally, we discuss recent advances on the key subcellular and molecular players involved in topographical sensing. Throughout the review, we focus particularly on neuronal cells, whose unique morphology and behavior have inspired a large body of studies in the field of topographical sensing and revealed fascinating cellular mechanisms. We conclude by using the current understanding of the cell-topography interactions at different scales as a springboard for identifying future challenges in the field of contact guidance.

Highlights

  • Throughout the whole life of multicellular organisms, cells live, and achieve their functions embedded in a highly complex and sometimes evolving 3D environment

  • contact guidance appears mediated by a complex cross-talk between FA maturation

  • it is now clear that the physical properties of the extracellular environment

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Summary

Introduction

Throughout the whole life of multicellular organisms, cells live, and achieve their functions embedded in a highly complex and sometimes evolving 3D environment. The influence of external cues on cell function and behavior has long been envisioned mainly from a biochemical point of view (e.g., via the action of small chemicals, morphogens, hormones, growth factors, etc.). It is clear that the physical properties of the extracellular environment, stiffness or topography for instance, play a crucial role in modulating cell morphology and major cell functions such as proliferation, differentiation, polarization, and migration. The topography of the extracellular environment can be defined as the size, shape, and organization of structural elements present around cells. Most cells are surrounded by the extracellular matrix (ECM). The ECM of different tissues such as blood vessel, bone, cartilage, or nerve are composed of micro and nanoscale topographic features with which cells can interact

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