Spatio-Temporal Control of Cell Adhesion: Toward Programmable Platforms to Manipulate Cell Functions and Fate

Abstract

Biophysical and biochemical signals of material surfaces potently regulate cell functions and fate. In particular, micro- and nano-scale patterns of adhesion signals can finely elicit and affect a plethora of signaling pathways ultimately affecting gene expression, in a process known as mechanotransduction. Our fundamental understanding of cell-material signals interaction and reaction is based on static culturing platforms, i.e., substrates exhibiting signals whose configuration is time-invariant. However, cells in-vivo are exposed to arrays of biophysical and biochemical signals that change in time and space and the way cells integrate these might eventually dictate their behavior. Advancements in fabrication technologies and materials engineering, have recently enabled the development of culturing platforms able to display patterns of biochemical and biophysical signals whose features change in time and space in response to external stimuli and according to selected programmes. These dynamic devices proved to be particularly helpful in shedding light on how cells adapt to a dynamic microenvironment or integrate spatio-temporal variations of signals. In this work, we present the most relevant findings in the context of dynamic platforms for controlling cell functions and fate in vitro. We place emphasis on the technological aspects concerning the fabrication of platforms displaying micro- and nano-scale dynamic signals and on the physical-chemical stimuli necessary to actuate the spatio-temporal changes of the signal patterns. In particular, we illustrate strategies to encode material surfaces with dynamic ligands and patterns thereof, topographic relieves and mechanical properties. Additionally, we present the most effective, yet cytocompatible methods to actuate the spatio-temporal changes of the signals. We focus on cell reaction and response to dynamic changes of signal presentation. Finally, potential applications of this new generation of culturing systems for in vitro and in vivo applications, including regenerative medicine and cell conditioning are presented.

Electrophoretic Deposition and Characterization of Functional Coatings Based on an Antibacterial Gallium (III)-Chitosan Complex

“…Since CS has been reported to be non-toxic to MG-63 cells [75], the reason for this decreased viability could be related to the relatively low number of attached cells. It is common knowledge that cell adhesion first involves non-specific forces, such as electrostatic or van der Waals forces, followed by specific (i.e., receptor-mediated) interactions of the cell with the substrate [76]. Non-specific electrostatic interactions between protonated amine groups from the glucosamine unit in CS and negatively charged carboxylate and sulfate groups in cell surface proteoglycans are responsible for cell adhesion to CS [77].…”

Hierarchical Micro-Nano Topography Promotes Cell Adhesion and Osteogenic Differentiation via Integrin α2-PI3K-AKT Signaling Axis

“…In the past few years, there has been growing interest in the effects of different surface features at various scales on cell adhesion, proliferation, and osteogenic differentiation (Anselme et al, 2010;Chen et al, 2014;Li et al, 2016;Skoog et al, 2018;Zhang et al, 2019). It is well recognized that micro-scale structures ensure the initial stability of the implant and promote the bone locking (Saruta et al, 2019), while nano-scale structures have more significant effects on the adhesion and differentiation of cells (Kim et al, 2013;Gorelik and Gautreau, 2014;Cimmino et al, 2018). Furthermore, it has been illustrated that the regulatory effect of nano-scale structures is precisely based on the mechanical retention provided by the micro-scale structures, i.e., the initial stability of intraosseous implants (Deng et al, 2019).…”

The Role of Stiffness in Cell Reprogramming: A Potential Role for Biomaterials in Inducing Tissue Regeneration

“…Many pieces of evidence indicate that a combination of dimensions influences focal adhesion dynamics, suggesting a possible common mechanic response of cells to topographic parameters of substrates. It has been shown how the geometry of the substrate may affect focal adhesion orientation as well as their formation [136]. Focal adhesions orientation determines cytoskeletal dynamics orienting stress fiber.…”