Cell–Cell Adhesion-Driven Contact Guidance and Its Effect on Human Mesenchymal Stem Cell Differentiation

Abstract

Contact guidance has been extensively explored using patterned adhesion functionalities that predominantly mimic cell–matrix interactions. Whether contact guidance can also be driven by other types of interactions, such as cell−cell adhesion, still remains a question. Herein, this query is addressed by engineering a set of microstrip patterns of (i) cell–cell adhesion ligands and (ii) segregated cell–cell and cell–matrix ligands as a simple yet versatile set of platforms for the guidance of spreading, adhesion, and differentiation of mesenchymal stem cells. It was unprecedently found that micropatterns of cell–cell adhesion ligands can induce contact guidance. Surprisingly, it was found that patterns of alternating cell–matrix and cell–cell strips also induce contact guidance despite providing a spatial continuum for cell adhesion. This guidance is believed to be due to the difference between the potencies of the two adhesions. Furthermore, patterns that combine the two segregated adhesion functionalities were shown to induce more human mesenchymal stem cell osteogenic differentiation than monofunctional patterns. This work provides new insight into the functional crosstalk between cell–cell and cell–matrix adhesions and, overall, further highlights the ubiquitous impact of the biochemical anisotropy of the extracellular environment on cell function.

Integrated Analysis of Single-Cell RNA-seq and Bulk RNA-seq in the Identification of a Novel ceRNA Network and Key Biomarkers in Diabetic Kidney Disease

“…Previous studies have shown that cell adhesion plays a vital role in a number of pathological processes, including the recirculation and movement of leukocytes, 39 cell differentiation, 40 and the activation of and communication between immune cells. 41 Furthermore, changes in the levels of adhesion molecules and cytokines have been detected in diabetic nephropathy and reported to represent vital mediators of injury in several types of glomerulonephritis and tubulointerstitial nephritis, thus underscoring their diagnostic roles in this renal microvascular complication.…”

Enhancement of Endothelialization by Topographical Features Is Mediated by PTP1B-Dependent Endothelial Adherens Junctions Remodeling

“…When subjected to luminal shear flows, focal adhesions in ECs undergo a rapid remodeling and alignment in the direction of the flow within a few minutes . Similarly, focal adhesions play key roles in sensing spatial features of the ECM, both independently or in conjunction with the cell–cell interactions. , For example, micrometer-sized patterns induce the reorganization of the actin cytoskeleton and FAs to orient cell movements and migrate. , …”

“…30 Similarly, focal adhesions play key roles in sensing spatial features of the ECM, both independently or in conjunction with the cell−cell interactions. 31,32 For example, micrometer-sized patterns induce the reorganization of the actin cytoskeleton and FAs to orient cell movements and migrate. 33,34 At the cell−cell interface, endothelial adherens junctions (EAJs) serve as the adhesive structures mediating the physical connection and the transmission of biomechanical signals between ECs.…”

Quantification and Imaging of Nanoscale Contact with Förster Resonance Energy Transfer

“…Adhesion between solid materials is crucial in several fields of biology, science, and technology, such as cellular adhesion and contact mechanics. − It is caused by intermolecular forces, like hydrogen bonding and van der Waals forces . These mechanisms are taking place up to a distance of 0.1–0.4 nm , and, thus, require nanoscale contact (NSC) between the adhering surfaces. , As a result, an increase in nanoscale contact area (NSCA) leads to an increase in adhesion between surfaces. − …”