Papers by Andreas Kourouklis
In working towards the goal of mimicking multiple features of the extracellular matrix (ECM), we ... more In working towards the goal of mimicking multiple features of the extracellular matrix (ECM), we developed a strategy to create adhesive protein patterns on polymer films with tunable viscous characteristics. The block copolymer films are generated by interfacial self-assembly with the presentation of dopant homopolymer, since the concentration of the latter is known to affect the lateral mobility of the film. The supported polymer films are subsequently surface-modified by microcontact printing using fibronectin (FN), yielding material surfaces which can potentially display independent control over mechanical and adhesive properties. This work demonstrates a new method for the design of materials with the potential to recapitulate the viscous component of the ECM in future in vitro studies.
Cellular and Molecular Bioengineering, 2015
The relationship between substrate properties and cell behavior is complex, including roles for b... more The relationship between substrate properties and cell behavior is complex, including roles for both mechanics and biochemistry. Here we investigate the role of viscous dissipation on cell adhesion behaviors, using polymer films of tunable lateral mobility. We find that fibroblasts selectively use a v b 3 and a 5 b 1 integrin receptors to control their spreading area and polarization on low and high mobility films, respectively. In addition, the dynamics of cell spreading and polarization are well described by a semi-empirical sigmoidal relationship. Analysis of cell dynamic behavior reveals that spreading dynamics are controlled by the availability of integrins, whereas the polarization dynamics are controlled by intracellular signaling. The result that cells preferentially use specific integrin receptors in response to substrate mechanical properties has broad implications for processes in dynamic environments such as wound healing and cancer metastasis.
In contrast with the majority of substrates used to study cell adhesion, the natural extracellula... more In contrast with the majority of substrates used to study cell adhesion, the natural extracellular matrix (ECM) is dynamic and remodeled over time. Here we use amphiphilic block copolymers to create selfassembled supported films with tunable lateral mobility. These films are intended to serve as partial mimics of the ECM in order to better understand cell adhesion responses, specifically in the context of dynamic substrates. Block copolymers are end-labeled with RGD peptide ligands to allow for integrinmediated cell adhesion, and the addition of a trace hydrophobic homopolymer is used to control the film lateral mobility. We find that NIH 3T3 fibroblasts cultured on these biomimetic films exhibit nonlinear spreading behavior in response to substrate mobility. In the absence of RGD ligands, however, fibroblasts do not spread. Employing quantitative analysis of focal adhesions (FA) and integrin ligation, we discover the presence of FA-dependent and FA-independent mechanisms responsible for the biphasic cell spreading behavior. The use of designed biomimetic platforms therefore yields insight into ECM mechanosensing by revealing that cells can engage distinct mechanisms to promote adhesion onto substrates with different time-dependent properties.
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Papers by Andreas Kourouklis