Specific control of cell–material interactions: Targeting cell receptors using ligand-functionalized polymer substrates

Abstract

Cells respond to their environment in complex and sometimes poorly understood ways. Protein, peptide and synthetic peptidomimetic ligands may all be used to stimulate cells via receptor signaling, using interactions that are often highly specific. Polymer substrates that present these ligands provide a promising way to control cell development, both for applications in biotechnology and for fundamental studies of cell biology. Here we review a large range of techniques that have been employed to create and characterize ligandfunctionalized substrates, with a particular focus on techniques that allow specific and consistent stimulation.

Focal adhesion stabilization by enhanced integrin-cRGD binding affinity

“…Conformational changes caused by a flexible and/or too long spacer can result in the shielding of the active site [10,36,44,66]. In a recent study, we showed that the bulky and more rigid polyproline sequence used in compound 3 leads to a reduction in packing density when self-assembled on gold, compared with the alkane-based ligand [43].…”

“…In recent years, novel strategies were developed, based on the engineering of biomimetic matrices for controlled stimulation of cells in vitro, particularly in key biomedical applications such as stimulation of immune cells, controlling pluripotency and regulating cell migration [9,10]. The use of such surfaces enabled testing the effects of ECM ligands diversity, as well as the effects of integrin receptor occupancy and clustering [11].…”

“…polyglycine, polyproline) have been used as spacers for peptide immobilization. Nonetheless, despite their wide use, ligands bearing aliphatic and PEG spacers may experience a decrease in binding affinity [10,44]. Densely packed monolayers and spacer flexibility may prevent optimal exposure of the integrin ligands.…”

Physical cues of cell culture materials lead the direction of differentiation lineages of pluripotent stem cells

“…1). [7][8][9][10][11][12] However, investigators have only recently begun to evaluate the potential importance of physical cues on stem cell differentiation, such as cell shape, cell culture polymeric biomaterial stiffness, 13 mechanical force (e.g., shear stress imposed by culture media and cyclic stretching of biomaterials), 14 and external force (e.g., electrical forces, magnetic forces, and light signals) (Fig. 1).…”

Dynamic and Responsive Growth Factor Delivery from Electrospun and Hydrogel Tissue Engineering Materials

“…For example, extensive work has been done tuning material stiffness [5] and the nano/microscale morphology, [6] and these properties have both been shown to significantly affect cell differentiation and proliferation. [7] While tuning an individual biochemical or physical cue can enable study of its effect in isolation and enhance material performance, [8] multiple biomimetic cues often have a synergistic effect, such that the overall benefit is greater than the combined individual benefits. [7b,9] This makes it important to include and optimize as many aspects of the ECM as synthetically possible in order to achieve the greatest therapeutic benefit.…”