Unfolding IGDQ Peptides for Engineering Motogenic Interfaces

Abstract

Extracellular matrix (ECM)-mimicking surfaces are pivotal tools in understanding adherent cell physiopathology. In this sense, we have recently reported on a discrete set of ECM-mimicking SAMs, among which only those exposing IGDQ peptide-alkanethiols sustain the adhesion of MDA-MB-231 cells by triggering FAK phosphorylation and peculiarly induce the migration of individual cancer cells on the subcentimeter scale. Starting from the experimentally observed relationship among the SAM composition, organization, and biological response, a systematic computational characterization aided in pinpointing the atomistic details through which specific composition and organization achieve the desired biological responsiveness. Specifically, the solvent, number and type of peptides, and presence or absence of surface fillers were accurately considered, creating representative model SAMs simulated by means of classical molecular dynamics (MD) with a view toward unravelling the experimental evidence, revealing how the conformational and structural features of these substrates dictate the specific motogenic responses. Through complementary experimental and computational investigations, it clearly emerges that there exists a distinct and precise mutual interaction among IGDQ-peptides, the surface fillers, and Au, which controls the structural properties of the ECM-mimicking SAMs and thus their motogenic potential.

Hyaluronan (HA) Immobilized on Surfaces via Self-Assembled Monolayers of HA-Binding Peptide Modulates Endothelial Cell Spreading and Migration through Focal Adhesion

“…We developed mixed monolayers of HS-Pep-1 by mixing with 1-octanethiol to create SAMs with low (1%) and high (100%) density of Pep-1 on Au-coated substrates and then compared the HA binding ability on different densities of HS-Pep-1 (Figure B). While here we have created random mixed SAMs, it would be possible to create gradients of mixed monolayers as reported by Bonifazi and co-workers. , The thickness of SAMs was first measured by ellipsometry in air and subsequently in ultrapure water. 1-Octanethiol monolayers had thicknesses of 5.7 ± 0.2 nm in air and 5.5 ± 0.6 nm in water (Figure A1).…”

Peptide-based self-assembled monolayers (SAMs): what peptides can do for SAMs and vice versa

“…5b). 27,102,103 Peptide-SAMs have contributed greatly to develop ECM models. For instance, the work by Mrksich and collaborators has contributed to elucidate the role of peptide and protein ligands in cell-ECM interactions, by studying SAMs presenting RGD motifs with different packing densities and spacing to study the adhesion and spreading of different cell types.…”

“…Gradient surfaces display a steady variation of one or more physicochemical property in space which can also change over time. 17 Bonifazi and co-workers 27,103 developed uniform peptide monolayers based on the IGD epitope of FN and gradients through one-step immersion and gradual immersion using a linear-motion drive, 178 respectively. Gradients were formed through the co-assembly of thiol-containing IGDQ peptides anchored onto linkers of different length and hydrophilicity (e.g., hydrophilic undecyl-tetraethylene glycol (EG 4 ) chain and hydrophobic n-octanethiol) and corresponding linkers as backfiller molecules.…”

“…31 These molecular events also take place in peptide-based SAMs, and a number of strategies have been developed in order to improve spatiotemporal display of peptide signals, including the formation of patterns, 6 gradients, and dynamic surfaces. 27,102,103,114,174…”

“…5b). 103 Building dynamic peptide-SAMs that change their properties controllably in time requires the inclusion of chemical moieties that are sensitive to specific stimuli. Light, electrochemical and enzyme activation of SAMs have been exploited to generate desired and controlled responses, either in cell culture or in biosensing applications.…”