Topic 3: Interfacing supramolecular chemistry with cellular functions.

Cellular motility is nowadays well recognized as a key process involved in both physiological and pathological phenomena. In the immune system, an elaborate network of signaling directs leukocytes from the circulation into the surrounding tissue to destroy invading microorganisms and infected cells. In vertebrate adults, cell motility is a critical part of wound healing and tissue repair and it is also critical in disease states where the failure of migratory processes results in chronic inflammatory, vascular diseases, multiple sclerosis, and even mental retardation. Furthermore, aberrant cell migration in tumor invasion and metastasis is one the leading causes for cancer. Aiming at interfacing supramolecular chemistry with cell migration to govern its directionality, we very decided to explore this field, as it could lead to new paradigms to study new approaches for control cell growth, tumor invasion, and tissue regeneration. Physical and chemical cues such as the concentration gradients of signaling molecules are the main guiding stimuli for cell migration, inducing cell polarity and thus controlling the migration rate and direction.

Exploiting the haptotactic cellular response and taking advantage of the SAMs approach, we have engineered motogenic surfaces in which different cells displayed different migratory reactions. Contrary to the majority of the reports in which SAMs of Arginine-Glycine-Aspartic (RGD) peptides are used to induce migratory events as a consequence of a change of the surface adhesive properties, we have used for the first time the isoleucine-glycine-aspartic (IGD) peptidic motif present in the fibronectin gelating-binding domain. By preparing mixed SAMs on Au(111) exposing a chemical gradient of IGD-containing synthetic peptide, we could prepare for the first time motogenic surfaces displaying a truly macroscopic unidirectional migratory event of the deposited cells [Small, 2016, 12321]. By preparing mixed SAMs on Au(111) exposing a chemical gradient of IGD-containing synthetic peptide, we could prepare for the first time motogenic surfaces displaying a truly macroscopic unidirectional migratory event of the deposited cells. In particular, comparing the migratory response of human dermal fibroblasts (isolated from fetal skin, AG04431 skin HDFs) and cancer cells (MDA-MB-231, a model of human breast cancer), a different spatio-temporal migratory response could be observed for the two cellular typologies. Propelled by these achievements, we are now expanding our studies toward more complex systems in which bidirectional (or even multidirectional) cellular movements can be remotely controlled through external stimuli. Once achieved, future perspectives in this field will tackle the supramolecular modulation and control of the interactions between cells, aiming at triggering their interconnectivity and thus intercellular communications, essential actions for ruling a collective migratory behavior. In this respect, genetically-modified models cells are currently being investigated to interface specific receptor sites with artificial recognition units that are responsive toward an external stimulus.

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