Monolithic quartz platform for cellular contact guidance

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Research Letter

Monolithic quartz platform for cellular contact guidance Michael C. Robitaille, Joseph A. Christodoulides, and Jinny L. Liu, Naval Research Laboratory, 4555 Overlook Ave SW, Washington, DC 20375-5320, USA Wonmo Kang, School for Engineering of Matter, Transport and Energy, Arizona State University, Tempe, AZ 85287, USA Jeff M. Byers, Katarina Doctor, Dmitry Kozak, and Marc P. Raphael , Naval Research Laboratory, 4555 Overlook Ave SW, Washington, DC 20375-5320, USA Address all correspondence to Marc P. Raphael at [email protected] (Received 11 December 2019; accepted 28 February 2020)

Abstract Contact guidance is vital to many physiological processes, yet is still poorly understood. This is partly due to the variability of experimental platforms, making comparisons difficult. To combat this, a multiplexed approach was used to fabricate topographical cues on single quartz coverslips for high-throughput screening. Furthermore, this method offers control of surface roughness and protein adsorption characterization, two critical aspects to the in vitro environment often overlooked in contact guidance platforms. The quartz surface can be regenerated, is compatible with versatile microscopy modes, and can scale up for manufacturing offering a novel platform that could serve as a potential standard assay.

Introduction The phenomena of cellular response to topographical features, known as contact guidance, were first reported over a century ago[1] and has been shown to play crucial roles in a myriad of biological processes such as development,[2] wound healing,[3] cancer metastasis,[4] and in the performance of man-made biomaterials.[5] To elucidate cellular response to topographical properties, many groups have taken advantage of advances in micro/nanofabrication techniques to construct in vitro contact guidance platforms. Substrates are fabricated with a range of topographical feature sizes and geometries and are subsequently coated with extracellular matrix (ECM) proteins or peptides to promote cell adhesion, mimicking in vivo environments. Despite large research efforts spanning years to examine the cellular response to topographical cues, it remains difficult to see general trends in the literature. This is largely due to the fact that cellular response to environmental cues is heterogeneous in nature, and furthermore often depends upon the context in which the cues are presented to the cells. In terms of contact guidance, the resulting cell behavior varies dependent upon the cell type,[6] and even within a given cell type subtle conditions can directly alter the cellular response. For instance, Rajnicek et al. have shown that neurons of different embryonic ages respond differently to identical cues.[7] Furthermore, Teixeira et al. have shown that simply using different culture media can drastically change cellular orientation to identical contact guidance cues,[7,8] highlighting a crucial aspect of contact guidance environments often overlooked—the material surface interface. Indeed, the importan