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Stimuli-Responsive Mechanically Interlocked Peptide Rotaxanes for Biomaterials and Biosensing

Objetivo

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.

Ámbito científico (EuroSciVoc)

Palabras clave

Programa(s)

Tema(s)

Régimen de financiación

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

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Convocatoria de propuestas

(se abrirá en una nueva ventana) HORIZON-MSCA-2023-PF-01

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Coordinador

KUNGLIGA TEKNISKA HOEGSKOLAN
Aportación neta de la UEn
€ 206 887,68
Dirección
BRINELLVAGEN 8
100 44 Stockholm
Suecia
Región
Östra Sverige Stockholm Stockholms län
Tipo de actividad
Higher or Secondary Education Establishments
Enlaces
Coste total
Sin datos