Cancer cell–matrix interactions have been shown to enhance cancer cell survival via the activation of pro-survival signaling pathways. These pathways are initiated at the site of interaction, i.e., integrins, and thus, their inhibition has been the target of therapeutic strategies. Individual roles for fibronectin-binding integrin subtypes αvβ3 and α5β1 have been shown for various cellular processes; however, a systematic comparison of their function in adhesion-dependent chemoresistance is lacking. Here, we utilize integrin subtype-specific peptidomimetics for αvβ3 and α5β1, both as blocking agents on fibronectin-coated surfaces and as surface-immobilized adhesion sites, in order to parse out their role in breast cancer cell survival. Block copolymer micelle nanolithography is utilized to immobilize peptidomimetics onto highly ordered gold nanoparticle arrays with biologically relevant interparticle spacings (35, 50, or 70 nm), thereby providing a platform for ascertaining the dependence of ligand spacing in chemoprotection. We show that several cellular propertiesmorphology, focal adhesion formation, and migrationare intricately linked to both the integrin subtype and their nanospacing. Importantly, we show that chemotherapeutic drug sensitivity is highly dependent on both parameters, with smaller ligand spacing generally hindering survival. Furthermore, we identify ligand type-specific patterns of drug sensitivity, with enhanced chemosurvival when cells engage αvβ3 vs α5β1 on fibronectin; however, this is heavily reliant on nanoscale spacing, as the opposite is observed when ligands are spaced at 70 nm. These data imply that even nanoscale alterations in extracellular matrix properties have profound effects on cancer cell survival and can thus inform future therapies and drug testing platforms.

Cadherin mimetic peptides are widely used in synthetic biomaterials to mimic cell–cell adhesion in cell microniches. This mimicry regulates various cell behaviors. Although the interaction between immobilized cadherin and cells is investigated in numerous studies, the exact manner of functioning of cadherin mimetic peptides is yet to be fully understood. Cadherin mimetic peptides mimic only the critical amino acid sequence of cadherin and are not equal to these proteins in function. Compared to the cadherin proteins, mimetic peptides are more stable, easier to fabricate, and exhibit a precise chemical composition. In this study the E‐cadherin mimetic peptide His‐Ala‐Val (HAV) on material surfaces is immobilized and epithelial cell adhesion and clustering are studied. The results suggest that immobilized HAV peptides specifically interact with E‐cadherin on the cell membrane, resulting in an increased expression of E‐cadherin and its downstream signaling protein β‐catenin. This interaction relocates E‐cadherin‐based adhesion from the cell–cell interface to the cell–materials interface, which promotes cell adhesion via mechanosensing and initiates a transition in the cell cluster from a solid‐like to a fluid‐like state. The study presents an overview of the interactions between E‐cadherin mimetic peptide and epithelial cells to aid in the design of novel biomaterials.

Silicon nanowires are considered promising future biomedical sensors. However, their limited stability under physiological conditions poses a challenge in sensor development and necessitates a significantly improved knowledge of underlying effects as well as new solutions to enhance silicon nanowire durability. In the present study, we deduced the dissolution rates of silicon nanowires under simulated physiological conditions from atomic force microscopy measurements. We correlated the relevant change in nanowire diameter to changes in the electronic properties by examining the I-V characteristics of kinked silicon nanowire p–n junctions. Contact potential difference measurements and ambient pressure photoemission spectroscopy additionally gave insights into the electronic surface band structure. During the first week of immersion, the Fermi level of n-type silicon nanowires shifted considerably to higher energies, partly even above the conduction band edge, which manifested in an increased conductivity. After about a week, the Fermi level stabilized and the conductivity decreased consistently with the decreasing diameter caused by continuous nanowire dissolution. Our results show that a physiological environment can substantially affect the surface band structure of silicon nanowire devices, and with it, their electronic properties. Therefore, it is necessary to study these effects and find strategies to gain reliable biomedical sensors.