'Receptor clustering control and associated force sensing by surface patterning: when force matters'
This Editorial article is featured in the new Special Focus Issue 'Engineering the nanoenvironment for regenerative medicine' published by Nanomedicine (IF: 5.824)
“Nanostructured materials are ideally suited to study the impact that spatial
properties at the single molecule level have on cell adhesion.”
Dr Elisabetta Ada Cavalcanti-Adam & Professor Joachim Spatz (Max Planck Institute for
Intelligent Systems & University of Heidelberg, Germany).
Nanostructured and chemically functionalized materials which mimic architectural and mechanical features of natural cell microenvironments hold promise for a better understanding and control of cell physiological processes through molecular and nanoscale interactions. Ultimately, the design of defined scaffolds for tissue engineering based on these material properties will advance regenerative medicine. The clustering of transmembrane receptors into defined nanoscale structures triggers and regulates specific signaling networks with unprecedented precision and is involved in transducing forces between the cell and the matrix. Only few material-based technologies exist today that enable the local control of receptor clustering and are able to measure mechanotransduction-based cellular reactions. Receptor clustering and regulatory ligand–receptor interactions stimulate a variety of biological processes. Herein lies an opportunity for interdisciplinary efforts between the fields of engineering, chemistry and biology to design new materials with the aim of controlling and quantifying nanoscale and molecular interactions at cellular boundaries. These efforts, inspired by the cell microenvironment, have recently led to the creation of nanostructured surfaces for controlling and guiding cell adhesion and function in a predictable manner [1,2].
The cell microenvironment contains chemical and physical cues that arise from a complex, albeit defined, architecture of extracellular matrix networks. Achieving a defined spatial patterning of extracellular matrix cues at the nanoscale, while independently tuning the chemical and physical properties of surfaces, has been a challenge. Although the achievements made thus far have created a more detailed picture of how cells interact with their microenvironment, it has also raised new questions.
Current techniques used to investigate the effects of extracellular matrix ligand presentation on cell functions work by independently manipulating variables like ligand density, clustering and spacing [3–5]. The application of surfaces that present a specific spatial pattern of molecules and peptides at the nanoscale have elucidated the minimal requirements needed for activating signalling networks. In particular, strong interest has been devoted to understanding the spatial aspects of focal adhesion maturation, the assembly of discrete structures upon integrin binding to the extracellular matrix and large-scale clustering of hundreds of receptors. Focal adhesions transmit tensile stresses from the extracellular space to the cytoskeleton, thereby converting force cues into biochemical signals that regulate cell functions …..
To read this Editorial in full, please visit Nanomedicine’s website:
1.Shaw A, Lundin V, Petrova E et al. Spatial control of membrane receptor function using ligand nanocalipers. Nat. Methods 11(8), 841–846 (2014).
2.Martino MM, Briquez PS, Güç E et al. Growth factors engineered for super-affinity to the extracellular matrix enhance tissue healing. Science 343(6173), 885–888 (2014).
3.Deeg JA, Louban I, Aydin D, Selhuber-Unkel C, Kessler H, Spatz JP. Impact of local versus global ligand density on cellular adhesion. Nano Lett. 11(4), 1469–1476 (2011).
4.Arnold M, Cavalcanti-Adam EA, Glass R et al. Activation of integrin function by nanopatterned adhesive interfaces. Chemphyschem 5(3), 383–388 (2004).
5.Schvartzman M, Palma M, Sable J et al. Nanolithographic control of the spatial organization of cellular adhesion receptors at the single-molecule level. Nano Lett. 11(3), 1306–1312 (2011).
6.Geiger B, Spatz JP, Bershadsky AD. Environmental sensing through focal adhesions. Nat. Rev. Mol. Cell. Biol. 10(1), 21–33 (2009).
Nanomedicine: Special Focus Issue homepage:
Dr Elisabetta Ada Cavalcanti-Adam
Professor Joachim Spatz