Fibronectin-matrix sandwich-like microenvironments to manipulate cell fate

Ballester-Beltrán, José; Moratal, David; Lebourg, Myriam; Salmerón‐Sánchez, Manuel

doi:10.1039/c3bm60248f

Cited by 13 publications

(14 citation statements)

References 39 publications

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“…[22a,46b] FN in its globular conformation is unable to adequately facilitate cellular binding to adhesion and growth factor domains present on the molecule, while when adsorbed on PEA as nanonetworks it exposes these binding sites and enhanced cellular adhesion and signaling occur. [17a,47] Previous studies have showed that unmodified semicrystalline PLLA is unable to induce such structural changes in adsorbed FN, as we have confirmed here (Figure A). Indeed, while HFN7.1 antibodies are able to bind near the RGD domain on globular FN, as found on unmodified PLLA, only the structural conformation change provided by the addition of PEA brushes is able to expose the synergy binding domain recognized by mAb1937 (Figure F).…”

Section: Discussionmentioning

confidence: 83%

Functionalization of PLLA with Polymer Brushes to Trigger the Assembly of Fibronectin into Nanonetworks

Sprott

Ferrer

Dalby

et al. 2019

Adv Healthcare Materials

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Poly‐l‐lactic acid (PLLA) has been used as a biodegradable polymer for many years; the key characteristics of this polymer make it a versatile and useful resource for regenerative medicine. However, it is not inherently bioactive. Thus, here, a novel process is presented to functionalize PLLA surfaces with poly(ethyl acrylate) (PEA) brushes to provide biological functionality through PEA's ability to induce spontaneous organization of the extracellular matrix component fibronectin (FN) into physiological‐like nanofibrils. This process allows control of surface biofunctionality while maintaining PLLA bulk properties (i.e., degradation profile, mechanical strength). The new approach is based on surface‐initiated atomic transfer radical polymerization, which achieves a molecularly thin coating of PEA on top of the underlying PLLA. Beside surface characterization via atomic force microscopy, X‐ray photoelectron spectroscopy and water contact angle to measure PEA grafting, the biological activity of this surface modification is investigated. PEA brushes trigger FN organization into nanofibrils, which retain their ability to enhance adhesion and differentiation of C2C12 cells. The results demonstrate the potential of this technology to engineer controlled microenvironments to tune cell fate via biologically active surface modification of an otherwise bioinert biodegradable polymer, gaining wide use in tissue engineering applications.

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Section: Discussionmentioning

confidence: 83%

Functionalization of PLLA with Polymer Brushes to Trigger the Assembly of Fibronectin into Nanonetworks

Sprott

Ferrer

Dalby

et al. 2019

Adv Healthcare Materials

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“…The stimulation of dorsal receptors within the sandwich-like culture triggers changes in cell morphology, cell adhesion and intracellular signaling pathways (e.g. focal adhesion kinase, FAK) [10][11][12] . As an example, fibroblasts cultured within the sandwich-like system overexpressed the α 5 integrin subunit compared to the 2D, as observed for other 3D cultures 15,16 .…”

Section: Representative Resultsmentioning

confidence: 99%

Sandwich-like Microenvironments to Harness Cell/Material Interactions

Ballester-Beltrán

Lebourg

Salmerón‐Sánchez

2015

JoVE

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Cell culture has been traditionally carried out on bi-dimensional (2D) substrates where cells adhere using ventral receptors to the biomaterial surface. However in vivo, most of the cells are completely surrounded by the extracellular matrix (ECM), resulting in a three-dimensional (3D) distribution of receptors. This may trigger differences in the outside-in signaling pathways and thus in cell behavior. This article shows that stimulating the dorsal receptors of cells already adhered to a 2D substrate by overlaying a film of a new material (a sandwich-like culture) triggers important changes with respect to standard 2D cultures. Furthermore, the simultaneous excitation of ventral and dorsal receptors shifts cell behavior closer to that found in 3D environments. Additionally, due to the nature of the system, a sandwich-like culture is a versatile tool that allows the study of different parameters in cell/material interactions, e.g., topography, stiffness and different protein coatings at both the ventral and dorsal sides. Finally, since sandwich-like cultures are based on 2D substrates, several analysis procedures already developed for standard 2D cultures can be used normally, overcoming more complex procedures needed for 3D systems.

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“…We, among others, have been involved in the research of new alternatives for sandwich cultures, such as the use of ventral and dorsal surfaces with different properties/characteristics (e.g., stiffness and/or topological patterns) (Ballester-Beltrán et al, 2015). This system has shown cell morphology to be related to substrate rigidity and the ability of cells to reorganize ECM proteins adsorbed to these surfaces (Beningo et al, 2004;Ballester-Beltran et al, 2012b;Ballester-Beltrán et al, 2014). Furthermore, it has been shown that sandwich-like cultures can modify cell spreading/elongation and migration rates depending on the substrates properties, resulting in closer 3D environment behaviors (Beningo et al, 2004;Ballester-Beltrán et al, 2015).…”

Section: Solid Phase Stimulationmentioning

confidence: 99%

Sensing the Difference: The Influence of Anisotropic Cues on Cell Behavior

et al. 2015

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From tissue morphogenesis to homeostasis, cells continuously experience and respond to physical, chemical, and biological cues commonly presented in gradients. In this article, we focus our discussion on the importance of nano/micro topographic cues on cell activity, and the role of anisotropic milieus play on cell behavior, mostly adhesion and migration. We present the need to study physiological gradients in vitro. To do this, we review different cell migration mechanisms and how adherent cells react to the presence of complex tissue-like environments and cell-surface stimulation in 2D and 3D (e.g., ventral/dorsal anisotropy).

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Fibronectin-matrix sandwich-like microenvironments to manipulate cell fate

Abstract: Conventional 2D substrates fail to represent the natural environment of cells surrounded by the 3D extracellular matrix (ECM).

Cited by 13 publications

References 39 publications

Functionalization of PLLA with Polymer Brushes to Trigger the Assembly of Fibronectin into Nanonetworks

Functionalization of PLLA with Polymer Brushes to Trigger the Assembly of Fibronectin into Nanonetworks

Sandwich-like Microenvironments to Harness Cell/Material Interactions

Sensing the Difference: The Influence of Anisotropic Cues on Cell Behavior

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