Please release me: Electrochemically activated cell release is achieved using a redox‐active supramolecular complex (see picture). Host molecule CB[8] (green) links surface‐bound viologen (purple) with solution‐exposed RGD peptides (red). Electrochemical reduction dissociates the complex, releases the peptides, and thus releases the cells from the substrates. This supramolecular strategy is also applicable to microelectrodes.

This article reviews the state of the art in the development of strategies for generating supramolecular systems for dynamic cell studies. Dynamic systems are crucial to further our understanding of cell biology and are consequently at the heart of many medical applications. Increasing interest has therefore been focused recently on rendering systems bioactive and dynamic that can subsequently be employed to engage with cells. Different approaches using supramolecular chemistry are reviewed with particular emphasis on their application in cell studies. We conclude with an outlook on future challenges for dynamic cell research and applications.

Supramolecular control of adhesion of cells is demonstrated using synthetic integrin binding RGD peptide-ferrocene conjugates that were immobilized via host-guest chemistry onto cucurbit[7]uril coated gold surfaces.

Biomimetic and stimuli-responsive cell-material interfaces are actively being developed to study and control various cell-dynamics phenomena. Since cells naturally reside in the highly dynamic and complex environment of the extracellular matrix, attempts are being made to replicate these conditions in synthetic biomaterials. Supramolecular chemistry, dealing with noncovalent interactions, has recently provided possibilities to incorporate such dynamicity and responsiveness in various types of architectures. Using a cucurbit[8]uril-based host–guest system, we have successfully established a dynamic and electrochemically responsive interface for the display of the integrin-specific ligand, Arg-Gly-Asp (RGD), to promote cell adhesion. Due to the weak nature of the noncovalent forces by which the components at the interface are held together, we expected that cell adhesion would also be weaker in comparison to traditional interfaces where ligands are usually immobilized by covalent linkages. To assess the stability and limitations of our noncovalent interfaces, we performed single-cell force spectroscopy studies using fluid force microscopy. This technique enabled us to measure rupture forces of multiple cells that were allowed to adhere for several hours on individual substrates. We found that the rupture forces of cells adhered to both the noncovalent and covalent interfaces were nearly identical for up to several hours. We have analyzed and elucidated the reasons behind this result as a combination of factors including the weak rupture force between linear Arg-Gly-Asp and integrin, high surface density of the ligand, and increase in effective concentration of the supramolecular components under spread cells. These characteristics enable the construction of highly dynamic biointerfaces without compromising cell-adhesive properties.

Osteoclasts are responsible for bone resorption and implant surface roughness promotes osseointegration. However, little is known about the effect of roughness on osteoclast activity. This study aims at the characterization of osteoclastic response to surface roughness. The number of osteoclasts, the tartrate-resistant acid phosphatase and matrix metalloproteinase (MMP) activities, the cell morphology and the actin-ring formation were examined on smooth (TS), acid-etched (TA) and sandblasted acid-etched (TLA) titanium and on native bone. Cell morphology was comparable on TA, TLA and bone, actin rings being similar in size on TLA and bone, but smaller on TA and virtually absent on TS. Gelatin zymography revealed increased proMMP-9 expression on TA, TLA, and bone compared to TS. In general, osteoclasts show similar characteristics on rough titanium surfaces and on bone, but reduced activity on smooth titanium surfaces. These results offer some insight into the involvement of osteoclasts in remodeling processes around implant surfaces.