Enzyme-Activated RGD Ligands on Functionalized Poly(ethylene glycol) Monolayers: Surface Analysis and Cellular Response

Todd, Simon J.; Scurr, David J.; Gough, Julie E.; Alexander, Morgan R.; Ulijn, Rein V.

doi:10.1021/la900376h

Cited by 61 publications

(85 citation statements)

References 44 publications

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“…The extensive suite of proteases and protease recognition sites-any of which could be introduced into the sequence at one or more arbitrary positions-should provide a versatile toolbox for controlling IDP brush properties in a dynamic and specific manner. Analogous enzymatically addressable materials have been explored for a variety of applications such as payload delivery 42 , diagnostic monitoring 43 and ligand presentation [44][45][46] . Although much effort has been focused on understanding the biological function of endogenous IDPs, our study suggests that these proteins represent an untapped resource for biomaterial design.…”

Section: Discussionmentioning

confidence: 99%

Stimuli-sensitive intrinsically disordered protein brushes

et al. 2014

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Grafting polymers onto surfaces at high density to yield polymer brush coatings is a widely employed strategy to reduce biofouling and interfacial friction. These brushes almost universally feature synthetic polymers, which are often heterogeneous and do not readily allow incorporation of chemical functionalities at precise sites along the constituent chains. To complement these synthetic systems, we introduce a biomimetic, recombinant intrinsically disordered protein that can assemble into an environment-sensitive brush. This macromolecule adopts an extended conformation and can be grafted to solid supports to form oriented protein brushes that swell and collapse dramatically with changes in solution pH and ionic strength. We illustrate the value of sequence specificity by using proteases with mutually orthogonal recognition sites to modulate brush height in situ to predictable values. This study demonstrates that stimuli-responsive brushes can be fabricated from proteins and introduces them as a new class of smart biomaterial building blocks.

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Section: Discussionmentioning

confidence: 99%

Stimuli-sensitive intrinsically disordered protein brushes

et al. 2014

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“…73 The polymer hydrogel was shown to be sensitive to cell-secreted enzymes, thus establishing the concept of cell-responsive biomaterials. Subsequently, enzyme responsiveness was also accomplished on 2D surfaces, 74,75 leading to the development of peptide surfaces that respond to cell secreted phosphatase. 76 This now paves the way for interactive biomaterials wherein both the material and the cells are able to dynamically respond to stimuli presented by the respective other system.…”

Section: Biomaterials Evolutionmentioning

confidence: 99%

“…To mimic the dynamic variation of the display of biomolecules such as cell adhesion receptor ligands in the ECM and modulate more specific cell-material interactions, the presentation of biomolecules on material surfaces may also be varied in response to a stimulus. 74,[86][87][88][89] Finally, to mimic the ability of the ECM to dynamically change its structure, surfaces with stimuli induced changes in topography and elasticity are desirable. [90][91][92][93] Stability within the complex biological environment is another important aspect and is of major importance if long-term bio-interfaces are to be established.…”

Section: Materials Responsementioning

confidence: 99%

“…Figure 3 shows a representation of external stimuli; artificial changes in temperature, 91,92,107 the application of an electrical potential, 85,[108][109][110] the application of light 87,88,111,112 and mechanical forces 93,113 have all been used to trigger a dynamic change in either chemical or physical surface properties to affect the behaviour of cells. In addition, biomolecules that are naturally present in a biological environment -enzymes 74,76 and carbohydrates 89 for example -have been artificially added to systems to trigger a response of the biointerface.…”

Section: External Stimulimentioning

confidence: 99%

“…RGD based peptide sequences at the end of a PEG chain that is tethered to a glass surface were made inaccessible to cells by terminating the peptide with a sterically bulky fluorenylmethyloxycarbonyl (Fmoc) group. 74 Osteoblasts did not adhere to the Fmocterminated peptide surface, but when the blocking group was removed by enzymatic (elastase) cleavage of the terminal alanine-alanine sequence, the RGD sequence became accessible and cell adhesion was possible.…”

Section: Attachmentmentioning

confidence: 99%

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Regulation of Stem Cell Fate by Nanomaterial Substrates

Mashinchian

Turner

Dalby

et al. 2015

Nanomedicine (Lond.)

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Major design aspects for novel biomaterials are driven by the desire to mimic more varied and complex properties of a natural cellular environment with man-made materials. The development of stimulus responsive materials makes considerable contributions to the effort to incorporate dynamic and reversible elements into a biomaterial. This is particularly challenging for cell-material interactions that occur at an interface (biointerfaces); however, the design of responsive biointerfaces also presents opportunities in a variety of applications in biomedical research and regenerative medicine. This review will identify the requirements imposed on a responsive biointerface and use recent examples to demonstrate how some of these requirements have been met. Finally, the next steps in the development of more complex biomaterial interfaces, including multiple stimuli responsive surfaces, surfaces of 3D objects and interactive biointerfaces will be discussed.

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Stimuli‐Responsive Surfaces in Biomedical Applications

Pranzetti¹,

Preece²,

Mendes³

2013

Intelligent Stimuli‐Responsive Materials

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Nature provides mechanisms that are able to dynamically control specific and nonspecific interactions between cells and biological surfaces [1,2]. Scientists have long tried to reproduce these dynamic biological events and have recently made an important step in that direction by creating artificial stimuli-responsive surfaces [3][4][5][6][7]. These smart substrates present modulatory surface properties that are able to respond to external chemical/biochemical [8][9][10][11][12], thermal [13][14][15], electrical [16][17][18][19][20], and optical stimuli [21][22][23][24][25][26][27][28][29][30][31]. Due to their dynamic nature such substrates are very appealing for applications in the biomedical field [32]. Progress to date has led to control over biomolecule activity [33] and immobilization of a diverse array of proteins, including enzymes [34] and antibodies [35]. These prior achievements have encouraged researchers to take the challenge of using dynamic surfaces to modulate larger and more complex systems, such as bacteria [36] and mammalian cells [37].Achieving control over surface properties could provide new insights in the understanding of cell behavior and can offer distinct benefits with regard to the development of medical devices. For instance, the modulation of cell attachment and detachment could lead to the prevention of unwanted bacteria fouling on implants, reducing the risk of infections and rejection [38][39][40][41][42]. Furthermore, dynamic surfaces able to present on demand regulatory signals to a cell could provide unprecedented opportunities in studies of cell responses in real-time. Cells in tissues adhere to and interact with their extracellular environment via specialized cell-cell and cell-extracellular

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Enzyme-Activated RGD Ligands on Functionalized Poly(ethylene glycol) Monolayers: Surface Analysis and Cellular Response

Cited by 61 publications

References 44 publications

Stimuli-sensitive intrinsically disordered protein brushes

Stimuli-sensitive intrinsically disordered protein brushes

Regulation of Stem Cell Fate by Nanomaterial Substrates

Stimuli‐Responsive Surfaces in Biomedical Applications

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