| AVS 58th Annual International Symposium and Exhibition | |
| Biofabrication and Novel Devices Focus Topic | Tuesday Sessions |
| Session BN-TuA |
| Session: | Biofabrication Methods and Devices |
| Presenter: | Shalom Wind, Columbia University |
| Authors: | S. Wind, Columbia University M. Schvartzman, Columbia University M. Palma, Columbia University M. Biggs, Columbia University T. Fazio, Columbia University R. Piqueras Jover, Columbia University M. Sheetz, Columbia University |
| Correspondent: | Click to Email |
The physical properties of a cell's environment are important factors in determining cell behavior and ultimately, phenotype. Two key factors that have been associated with major changes in cell morphology and behavior are (1) spatial organization of extracellular matrix (ECM) molecules and (2) rigidity. In order to understanding how cells sense these factors at the nanoscale and how these factors affect cell function, we have developed new nanofabricated surfaces in which these physical characteristics of the ECM are simulated.
The first type of surface combines nanoimprint lithography with selective biofunctionalization to precisely control the placement and geometric arrangement of integrin binding sites. The binding sites consist of sub-10 nm metallic nanodots functionalized with ECM binding ligands, designed so that each site can accommodate only a single integrin molecule. Cell spreading and motility assays were performed using 3T3 fibroblasts on arrays in which binding site spacing, density and number were independently varied. Cell spreading efficiency was markedly enhanced for clusters comprising at least 4 liganded sites spaced ≤ 60 nm apart, with little or no dependence on global density. This points to the existence of a minimal matrix adhesion unit defined in space and stoichiometry.
A second type of surface consists of elastomeric substrates with locally variable rigidity. We have found that exposure of poly(dimethylsiloxane) (PDMS) to an electron beam alters the rigidity of the elastomer, with the modulus of the exposed regions increasing with the applied electron dose. In addition to planar surfaces, pillared substrates can be patterned with no measurable change to the pillar dimensions. Immortalized mesenchymal stem cells plated on soft PDMS surfaces patterned in this manner displayed a distinct preference for the more rigid, exposed regions, forming focal adhesion nearly exclusively there. Furthermore, focal adhesion formation diminished significantly as the size of the exposed features was reduced below 1 μm, indicating that there is a length scale for cellular rigidity sensing, with the critical length in the range of a few hundred nanometers.
By adapting the tools of nanomanufacturing to cellular systems, we are able to define important parameters that can control aspects of cell function and behavior and will help identify conditions under which these functions may be altered. Potential applications range from therapeutic treatments that block metastasis to the development of new adoptive immunotherapies, as well as the development of new guidelines for the design of tissue scaffolds that can optimize healing without scarring.