Abstract
Well-controlled surfaces with immobilized substrates enable novel approaches to investigate specific aspects of biological processes related to cell adhesion or motility. A subset of integrins, cellular transmembrane glycoproteins, recognize the evolutionarily conserved tripeptide sequence RGD, and anchor cells to their surrounding proteins as well as mediate bidirectional signaling. In this study, the main question was how co-presentation of hyaluronan (HA), an essential component of the extracellular matrix (ECM), and the RGD motif affect integrin binding. We report a method to prepare self-assembled monolayers on gold surfaces, co-presenting the cell adhesive RGD motif and small HA molecules, to investigate integrin containing proteoliposome binding. This technique enables an independent adjustment of the RGD motif and HA density while maintaining a passivating background: Layer formation and subsequent interactions with αIIbβ3 integrins, which are reconstituted in liposomes, was monitored by label-free quartz crystal microbalance with dissipation monitoring (QCM-D). Exceeding a critical RGD motif density of 40% results in enhanced binding of proteoliposomes. Co-presentation studies with varying HA and constant RGD motif density demonstrate that marginal amounts of HA are sufficient to prevent integrin binding. These findings are of specific importance in relation to cancer cell microenvironments, which show highly enriched HA in the surrounding ECM to reduce adhesion properties.
Highlights
Nature has generated well-adapted processes and materials through natural selection
In order to understand the role of HA in the dynamic process of cell adhesion, we aim to establish a synthetic model with reduced complexity, giving us the opportunity to focus on the repulsive forces of HA
Within this study a biomimetic model was established to address the challenge of co-presenting HA and the RGD motif to study integrin binding
Summary
Nature has generated well-adapted processes and materials through natural selection. Nature in its remarkable diversity provides an extraordinary collection of strategies. These can be exploited as a source of inspiration and adopted for biological applications. One approach to utilize this synthetic biological concept is the “bottom-up” approach, in which a minimal number of synthetic or biological molecules are combined to realize a desired function (Tu and Tirrell, 2004; Benner and Sismour, 2005; Purnick and Weiss, 2009). Molecular biomaterials can be fabricated in a “bottom-up” approach, in which molecules adapt a defined arrangement and produce novel macromolecular assemblies. Molecular assembly can be applied to modulate surface properties of a material’s interface, where chemical, physical, and biological processes
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