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Abstract Although mechanical signals presented by the extracellular matrix are known to regulate many essential cell functions, the specific effects of these interactions, particularly in response to dynamic and heterogeneous cues, remain largely unknown. Here, a modular semisynthetic approach is introduced to create protein–polymer hydrogel biomaterials that undergo reversible stiffening in response to user‐specified inputs. Employing a novel dual‐chemoenzymatic modification strategy, fusion protein‐based gel crosslinkers are created that exhibit stimuli‐dependent intramolecular association. Linkers based on calmodulin yield calcium‐sensitive materials, while those containing the photosensitive light, oxygen, and voltage sensing domain 2 (LOV2) protein give phototunable constructs whose moduli can be cycled on demand with spatiotemporal control about living cells. These unique materials are exploited to demonstrate the significant role that cyclic mechanical loading plays on fibroblast‐to‐myofibroblast transdifferentiation in 3D space. The moduli‐switchable materials should prove useful for studies in mechanobiology, providing new avenues to probe and direct matrix‐driven changes in 4D cell physiology.
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Logic‐Based Delivery of Site‐Specifically Modified Proteins from Environmentally Responsive Hydrogel Biomaterials
Abstract The controlled presentation of proteins from and within materials remains of significant interest for many bioengineering applications. Though “smart” platforms offer control over protein release in response to a single external cue, no strategy has been developed to trigger delivery in response to user‐specified combinations of environmental inputs, nor to independently control the release of multiple species from a homogenous material. Here, a modular semisynthetic scheme is introduced to govern the release of site‐specifically modified proteins from hydrogels following Boolean logic. A sortase‐mediated transpeptidation reaction is used to generate recombinant proteins C‐terminally tethered to gels through environmentally sensitive degradable linkers. By varying the connectivity of multiple stimuli‐labile moieties within these customizable linkers, YES/OR/AND control of protein release is exhaustively demonstrated in response to one and two‐input combinations involving enzyme, reductant, and light. Tethering of multiple proteins each through a different stimuli‐sensitive linker permits their independent and sequential release from a common material. It is expected that these methodologies will enable new opportunities in tissue engineering and therapeutic delivery.
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- PAR ID:
- 10460198
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Advanced Materials
- Volume:
- 31
- Issue:
- 33
- ISSN:
- 0935-9648
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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