How stiff and thin can an engineered extracellular matrix be? Modeling molecular forces at the cell-matrix interface

Walton, Emily B.; Oommen, Binu; Vliet, Krystyn J. Van

doi:10.1109/iembs.2007.4353825

Cited by 3 publications

(5 citation statements)

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“…This gradual masking of mechanoselective adhesion is consistent with previous studies on eukaryotic cells but is observed here after addition of just a single compliant polyelectrolyte layer; decreased adhesion of fibroblasts is not observed until addition of at least five bilayers of the compliant PEM to the stiff PEM. This may be attributed in part to the increased forces and distances over which eukaryotic cells can strain the underlying substrata through actomyosin traction at focal adhesions of diameters comparable to a single bacterium. , …”

Section: Resultsmentioning

confidence: 99%

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Substrata Mechanical Stiffness Can Regulate Adhesion of Viable Bacteria

et al. 2008

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The competing mechanisms that regulate adhesion of bacteria to surfaces and subsequent biofilm formation remain unclear, though nearly all studies have focused on the role of physical and chemical properties of the material surface. Given the large monetary and health costs of medical-device colonization and hospital-acquired infections due to bacteria, there is considerable interest in better understanding of material properties that can limit bacterial adhesion and viability. Here we employ weak polyelectrolyte multilayer (PEM) thin films comprised of poly(allylamine) hydrochloride (PAH) and poly(acrylic acid) (PAA), assembled over a range of conditions, to explore the physicochemical and mechanical characteristics of material surfaces controlling adhesion of Staphylococcus epidermidis bacteria and subsequent colony growth. Although it is increasingly appreciated that eukaryotic cells possess subcellular structures and biomolecular pathways to sense and respond to local chemomechanical environments, much less is known about mechanoselective adhesion of prokaryotes such as these bacteria. We find that adhesion of viable S. epidermidis correlates positively with the stiffness of these polymeric substrata, independently of the roughness, interaction energy, and charge density of these materials. Quantitatively similar trends observed for wild-type and actin analogue mutant Escherichia coli suggest that these results are not confined to only specific bacterial strains, shapes, or cell envelope types. These results indicate the plausibility of mechanoselective adhesion mechanisms in prokaryotes and suggest that mechanical stiffness of substrata materials represents an additional parameter that can regulate adhesion of and subsequent colonization by viable bacteria.

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Section: Resultsmentioning

confidence: 99%

“…This may be attributed in part to the increased forces and distances over which eukaryotic cells can strain the underlying substrata through actomyosin traction at focal adhesions of diameters comparable to a single bacterium. 53,54 3.5. Mechanoselective Adhesion is Independent of Monovalent Ion Concentration.…”

Section: S Epidermidis Adhesion Modulatedmentioning

confidence: 99%

Substrata Mechanical Stiffness Can Regulate Adhesion of Viable Bacteria

et al. 2008

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“…Accordingly, it is becoming increasingly clear that the development of functional in vitro models of tissue patho/physiology depends on the ability to understand, predict, and harness the chemical and mechanical properties of extracellular substrata [1,2]. Several descriptive studies have highlighted the cooperative effects of ligand presentation and substrata stiffness on cellular functions ranging from adhesion and motility to morphogenesis and remodeling [3,4]; furthermore, these findings have led to the development of new synthetic substrata offering improved control over independent biochemical and mechanical cues [5-12]. In particular, poly (acrylamide) (PA) hydrogels of approximate elastic modulus ( E ) of 10 1 –10 5 Pa have been surface-functionalized with adhesion proteins or ligands, and used extensively to study chemo-mechanical effects on a variety of cell fate processes including fibroblast migration and contractility [5], endothelial cell adhesion [6,7], myotube formation [8], stem cell differentiation [9], and hepatocyte spreading [10].…”

Section: Introductionmentioning

confidence: 99%

“…Polyethylene glycol (PEG)-based substrata exhibiting similar E comparable to those of PA hydrogels have also been used to evaluate the effects of mechanical compliance on cellular morphology and phenotype [11]. However, because changes in composition or extent of crosslinking in natural and aforementioned synthetic systems may also affect surface ligand density, configurations, and distensibility [12], the interplay between biochemical and mechanical cues on cellular fates has not yet been fully decoupled. A system amenable to independent modulation of chemical composition, stiffness, and ligand presentation has the potential to help elucidate the mechanisms of cooperative chemomechanical feedback, as well as aid in the development of highly functional in vitro models of tissues.…”

Section: Introductionmentioning

confidence: 99%

Modulation of hepatocyte phenotype in vitro via chemomechanical tuning of polyelectrolyte multilayers

et al. 2009

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It is increasingly appreciated that since cell and tissue functions are regulated by chemomechanical stimuli, precise control over such stimuli will improve the functionality of tissue models. However, due to the inherent difficulty in decoupling these cues as presented by extracellular materials, few studies have explored the independent modulation of biochemical and mechanical stimuli towards the manipulation of sustained cellular processes. Here, we demonstrate that both mechanical compliance and ligand presentation of synthetic, weak polyelectrolyte multilayers (PEMs) can be tuned independently to influence the adhesion and liver-specific functions of primary rat hepatocytes over extended in vitro culture (two weeks). These synthetic PEMs exhibited elastic moduli E ranging over 200 kPa -< E < 142 MPa, as much as one thousand-fold more compliant than tissue-culture polystyrene (E ∼ 2.5 GPa). The most compliant of these PEM substrata promoted hepatocyte adhesion and spheroidal morphology. Subsequent modification of PEMs with type I collagen and the proteoglycan decorin did not alter substrata compliance, but enhanced the retention of spheroids on surfaces and stabilized hepatic functions (albumin and urea secretion, CYP450 detoxification activity). Decorin exhibited unique compliance-mediated effects on hepatic functions, downregulating the hepatocyte phenotype when presented on highly compliant substrata while upregulating hepatocyte functions when presented on increasingly stiffer substrata. These results show that phenotypic functions of liver models can be modulated by leveraging synthetic polymers to study and optimize the interplay of biochemical and mechanical cues at the cell-material interface. More broadly, these results suggest an enabling approach for the systematic design of functional tissue models applied to drug screening, cell-based therapies and fundamental studies in development, physiology and disease.

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“…The results of the studies on cell functions during the tissue-specific homing process indicate that mechanical properties of the surrounding microenvironment are critical for regulating cell-ECM interactions. [113][114][115] Relevant cell-based assays can be carried out on plates coated for example, with ECM-derived integrin ligands. 116 Thus, the experimental models implementing cell exposure to molecules adsorbed on substrates enabled to demonstrate that collagens, laminins, 'RGD'-containing proteins (fibronectin, fibrin, vitronectin) as well as immunoglobulin superfamily proteins (VCAM, ICAMs) are capable of mediating cell adhesion.…”

Section: Using Chemotaxis Systems To Elucidate the Underlying Biologymentioning

confidence: 99%

The evolution of chemotaxis assays from static models to physiologically relevant platforms

et al. 2009

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The role of chemotactic gradients in the immunological response is an area which elicits a lot of attention due to its impact on the outcome of the inflammatory process. Consequently there are numerous standard in vitro designs which attempt to mimic chemotactic gradients, albeit in static conditions, and with no control over the concentration of the chemokine gradient. In recent times the design of the standard chemotaxis assay has incorporated modern microfluidic platforms, computer controlled flow devices and cell tracking software. Assays under fluid flow which use biochips have provided data which highlight the importance of shear stress on cell attachment and migration towards a chemokine gradient. However, the in vivo environment is far more complex in comparison to conventional cell assay chambers. The designs of biochips are therefore in constant flux as advances in technology permit ever greater imitations of in vivo conditions. Researchers are focused on designing a generation of new biochips and enhancing the physiological relevance of the current assays. The challenge is to combine a shear flow with a 3D scaffold containing the endothelial layer and permitting a natural diffusion of chemokines through a tissue-like basal matrix. Here we review the latest range of chemotaxis assays and assess the innovative features of their designs which enable them to better imitate the in vivo environment. We also present some alternative designs that were initially employed in tissue engineering which could potentially be used in the establishment of novel chemotaxis assays.

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How stiff and thin can an engineered extracellular matrix be? Modeling molecular forces at the cell-matrix interface

Cited by 3 publications

References 10 publications

Substrata Mechanical Stiffness Can Regulate Adhesion of Viable Bacteria

Substrata Mechanical Stiffness Can Regulate Adhesion of Viable Bacteria

Modulation of hepatocyte phenotype in vitro via chemomechanical tuning of polyelectrolyte multilayers

The evolution of chemotaxis assays from static models to physiologically relevant platforms

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