Abstract
Reciprocity between cells and their surrounding extracellular matrix is one of the main drivers for cellular function and, in turn, matrix maintenance and remodelling. Unravelling how cells respond to their environment is key in understanding mechanisms of health and disease. In all these examples, matrix anisotropy is an important element, since it can alter the cell shape and fate. In this work, the objective is to develop and exploit easy-to-produce platforms that can be used to study the cellular response to natural proteins assembled into diverse topographical cues. We demonstrate a robust and simple approach to form collagen substrates with different topographies by evaporating droplets of a collagen solution. Upon evaporation of the collagen solution, a stain of collagen is left behind, composed of three regions with a distinct pattern: an isotropic region, a concentric ring pattern, and a radially oriented region. The formation and size of these regions can be controlled by the evaporation rate of the droplet and initial collagen concentration. The patterns form topographical cues inducing a pattern-specific cell (tenocyte) morphology, density, and proliferation. Rapid and cost-effective production of different self-agglomerated collagen topographies and their interfaces enables further study of the cell shape-phenotype relationship in vitro. Substrate topography and in analogy tissue architecture remains a cue that can and will be used to steer and understand cell function in vitro, which in turn can be applied in vivo, e.g. in optimizing tissue engineering applications.
Highlights
Reciprocity between cells and their surrounding extracellular matrix is one of the main drivers for cellular function and, in turn, matrix maintenance and remodelling
Using Polarized Light Microscopy (PLM), we analysed the deposition patterns formed for different initial collagen concentrations and relative humidity
PLM images obtained from the center region are not included in Fig. 2 as the center region demonstrates more or less a flat homogenous characteristic
Summary
Reciprocity between cells and their surrounding extracellular matrix is one of the main drivers for cellular function and, in turn, matrix maintenance and remodelling. We demonstrate a robust and simple approach to form collagen substrates with different topographies by evaporating droplets of a collagen solution. Various in vitro platforms have been developed to study the relation between matrix structure or substrate topography and cell morphology and the resulting downstream responses. Production of such in vitro platforms often requires the use of advanced tools such as micro-contact printing3, electrospinning[4], or dip-pen n anolithography[5]. We present a robust and simple approach to generate complex collagen topographies consisting of isotropic and two kinds of anisotropic domains of different structures by evaporating collagen type I solution droplets. We explore the ability of different isotropic and anisotropic collagen patterns to steer cellular functions such as cell alignment, distribution, shape, and proliferation
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