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Stimuli-Responsive Mechanically Interlocked Peptide Rotaxanes for Biomaterials and Biosensing

Objective

Mechanically interlocked molecules (MIMs) feature mechanical bonds, which link multiple distinct components together allowing free movement between them without dissociation. This makes MIMs perfect candidates for artificial molecular machines, and earned them the Nobel Prize in Chemistry 2016. Over the last 30 years, MIMs have been applied in diverse areas from switchable catalysis to smart materials. However, they have so far only found limited use in biomedicine, due to the often lengthy synthesis and poor solubility in biological media. Directly addressing these challenges, we will use Natures own building blocks (i.e. peptides) to construct stimuli-responsive MIMs for use in bioapplications. Rotaxanes are a class of MIM resembling dumbbells, with a macrocyclic ring encircling the axle. We will use bioactive peptides as the rotaxane axle (making them intrinsically biocompatible MIMs) whose bioactivity will be initially silenced via obstruction of the encircled stimuli-responsive macrocycle, which acts as protective armour and stabilises the peptide. Upon application of a stimulus (e.g. light irradiation), self-immolative cleavage of the macrocycle occurs, liberating the free peptide. Hence, light acts as a stimulus to turn-on the bioactive response of the peptide on-demand. We will use this to design advanced biosensing systems for stimuli-responsive MMP2 cleavage of the peptide sequence PLGLAG. Further, we will develop beyond state-of-the-art photopatterning methods for cell adhesion, using the integrin-binding RGDS peptide sequence as our rotaxane axle. Using the high spatiotemporal control of light, we can turn on cell-adhesion where desired via self-immolation of the macrocycle using light irradiation. This action represents a precise, high-resolution method for the photopatterning of cell-adhesive biomaterials, a crucial first step for the use of peptide-coated biomaterials in therapeutics e.g. transplants, skin-grafts, and drug delivery platforms.

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Topic(s)

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-MSCA-2023-PF-01

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Coordinator

KUNGLIGA TEKNISKA HOEGSKOLAN
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 206 887,68
Address
BRINELLVAGEN 8
100 44 STOCKHOLM
Sweden

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Region
Östra Sverige Stockholm Stockholms län
Activity type
Higher or Secondary Education Establishments
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Total cost

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