Adhesion force spectroscopy with nanostructured colloidal probes reveals nanotopography-dependent early mechanotransductive interactions at the cell membrane level. Issue 27 (3rd July 2020)

• Record Type: Journal Article
• Authors: Chighizola, M.; Previdi, A.; Dini, T.; Piazzoni, C.; Lenardi, C.; Milani, P.; Schulte, C.; Podestà, A.
• Is Part Of: Nanoscale. Volume 12:Issue 27(2020)
• Page Start: 14708
• Page End: 14723
• Publication Date: 2020-07-03
• Subjects: Nanoscience -- Periodicals; Nanotechnology -- Periodicals; 620.505
• DOI: 10.1039/d0nr01991g
• Languages: English
• ISSNs: 2040-3364

Abstract

Abstract : The study shows, by exploiting a novel adhesion force spectroscopy approach, that microenvironmental nanotopography impacts strongly on integrin-mediated cellular mechanosensing, by influencing adhesion site force loading dynamics. Abstract : Mechanosensing, the ability of cells to perceive and interpret the microenvironmental biophysical cues (such as the nanotopography), impacts strongly cellular behaviour through mechanotransductive processes and signalling. These events are predominantly mediated by integrins, the principal cellular adhesion receptors located at the cell/extracellular matrix (ECM) interface. Because of the typical piconewton force range and nanometre length scale of mechanotransductive interactions, achieving a detailed understanding of the spatiotemporal dynamics occurring at the cell/microenvironment interface is challenging; sophisticated interdisciplinary methodologies are required. Moreover, an accurate control over the nanotopographical features of the microenvironment is essential, in order to systematically investigate and precisely assess the influence of the different nanotopographical motifs on the mechanotransductive process. In this framework, we were able to study and quantify the impact of microenvironmental nanotopography on early cellular adhesion events by means of adhesion force spectroscopy based on innovative colloidal probes mimicking the nanotopography of natural ECMs. These probes provided the opportunity to detect nanotopography-specific modulations of the molecular clutch force loading dynamics and integrin clustering at the level of single binding events, in the critical time window of nascent adhesion formation. Following this approach, we found that the nanotopographical features are responsible for an excessive force loading in single adhesion sites after 20–60 s of interaction, causing a drop in the number of adhesion sites. However, by manganese treatment we demonstrated that the availability of activated integrins is a critical regulatory factor for these nanotopography-dependent dynamics.