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.
Highlights
A major part of our understanding of cell biology is occupied by the effects of soluble signals on cell behavior
Cell adhesions have a direct impact on cytoskeleton arrangement, cell contractility, and nucleus shape, which altogether affect gene expression and eventually cell functions (Dalby et al, 2014; Murphy et al, 2014; Anderson et al, 2016; Ventre et al, 2018)
As soluble biochemical signals elicit very different cellular responses according to their dose and on the way they are delivered in time, do biophysical signals behave ? How does the variable spatio-temporal presentation of biophysical signals affect cell behavior? Does an optimal spatio-temporal presentation of bound signal to elicit a specific cell response in the most effective manner exist? Answering these questions may provide valuable insights for developing more effective and versatile culturing systems but might aid in shedding light on intricate biological processes involved whenever modifications in the microenvironment occur, for example in tissue and organ morphogenesis or in the development or progress of diseases
Summary
A major part of our understanding of cell biology is occupied by the effects of soluble signals (drugs, small molecules, peptides, proteins, growth factors) on cell behavior. Cell biologists usually relied on reductionist approaches to study cell-signal interactions in vitro seeking systems aimed at reducing the complexity of interactions or at eliciting specific cell responses to investigate cell-signal interplay These systems were instrumental to shape our understanding on the mechanisms underlying cell recognition and reaction to signals, but in most of the cases they are not able to capture specific aspects as multi signal stimulation or dynamic changes. Increasing the complexity of material substrate to control cell functions and fate in vitro with the introduction of dynamically changing signals would better mimic a natural context enabling the possibility to guide and stimulate cells with improved effectiveness.
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