Enzyme-Responsive Materials

Enzyme-responsive materials (ERMs) are a new class of smart materials that undergo macroscopic transitions when triggered by selective catalytic actions of enzymes. The use of enzymes as stimuli to trigger mechanical responses in materials opens up a number of possible applications in biology and medicine. Four classes of ERMs are studied in our group, based on supramolecular assemblies, chemically crosslinked hydrogel particles, nanoparticle assemblies and solid surfaces. Potential applications in regenerative medicine, diagnostics, and drug delivery are developed in close collaboration with industry.

[1] R.V. Ulijn. Enzyme responsive materials: a new class of smart biomaterials. J. Mat. Chem., 2006, 16, 2217-2225.
[2] R.V. Ulijn, N. Bibi, V. Jayawarna, P.D. Thornton, S.J. Todd, R.J. Mart, A.M. Smith, J.E. Gough, Bioresponsive hydrogels, Materials Today, April 2007, 10, 40-48.
[3] R.J. Mart, R.D. Osborne, M.M. Stevens, R.V. Ulijn, Peptide-Based Stimuli-Responsive Biomaterials. Soft Matter, 2, 822-835.

Enzyme Responsive Hydrogel Particles

We have developed a novel method to control the swelling of hydrogel particles, by exploiting molecular actuators based on peptides. This allows the overall charge on individual particles to be manipulated by enzymatic cleavage of a designed peptide sequence, releasing the charged residue and removing internal electrostatic repulsion and results in an increased mesh size, which reduces the accessibility of the interior of the bead to macromolecules.

[1] P. Thornton, G. McConnell, R.V. Ulijn, Enzyme responsive polymer hydrogel beads, Chem. Commun., 2005, 47, 5913-5915.
[2] P.D. Thornton, R.J. Mart, R.V. Ulijn, Enzyme-Responsive Polymer Hydrogel Particles for Controlled Release,  Adv. Mater., 2007, 19, 1352-1256.
[3] P.D. Thornton, R.J. Mart, S. Webb, R.V.Ulijn, Enzyme-Responsive Hydrogel Particles for the Controlled Release of Proteins: Designing Peptide Actuators to Match Payload, Soft Matter, 2008, 4, 821-827.
[4] T.O. McDonald, H. Qu, B.R. Saunders, R.V. Ulijn, Branched Peptide Actuators for Enzyme Responsive Hydrogel Particles, Soft Matter, 2009, in press.

Enzyme Responsive Surfaces

The aim of this work is to exploit enzyme reactions at the solid/liquid interface to control and direct cell behaviour. In living systems, the behaviour of cells (differentiation, migration, etc) is dictated by biochemical signals in the gel-like material that surrounds them. A number of these ligands are activated when required in response to enzymes that are secreted by the cells, thereby providing molecular feed-back systems that allow cells to adapt to their environment. We set out to mimic such a process in man-made material and develop surfaces that can be switched between a bio-inert and bioactive state in response to an enzyme.

[1] R.E. Rawsterne, S.J. Todd, J.E. Gough, D. Farrer, F. Rutten, M.R. Alexander, R.V. Ulijn, Cell Spreading Correlates with Log P of Surface Tethered Amino Acids, Acta Biomater., 2007, 3, 715-721.
[2] S.J. Todd, D. Farrar, J.E. Gough, R.V. Ulijn, Enzyme-Triggered Cell Attachment to Hydrogel Surfaces., Soft Matter, 2007, 3, 547-550.
[3] S.J. Todd, D.J. Scurr, J.E. Gough, M.R. Alexander, R.V. Ulijn, Enzyme-activated RGD ligands on functionalized PEG monolayers: surface analysis and cellular response, Langmuir, 2009, in press.