Biology subjects

Khoury, L. R.

Publications and source records attributed to Khoury, L. R..

3 recordsLinked to original sources

bioRxiv2026

Self-Terminating Bilayer Hydrogel Actuators via Enzyme-Programmed Mechanical Feedback

Autonomous soft materials that can actuate, perform a function, and then self-terminate without external intervention remain difficult to realize. Here, a bilayer hydrogel actuator fabricated by digital light processing-based 3D bioprinter is introduced that couples rapid thermoresponsive deformation with slower enzyme-programmed mechanical feedback to achieve self-regulated shape transformation and autonomous recovery. The system integrates a poly(N-isopropylacrylamide) actuation layer with a bovine serum albumin-poly(ethylene glycol) diacrylate enzyme-programmed layer loaded with trypsin. Above the lower critical solution temperature, deswelling of the actuation layer generates a strain mismatch across the bilayer and drives rapid closure. In parallel, proteolytic cleavage of albumin domains progressively softens the enzyme-programmed layer, reduces interlayer constraint, and acts as an intrinsic mechanical off-switch that relaxes curvature and restores the open state. This materials logic enables sustained enzyme release, time-dependent modulus loss, and autonomous shape recovery without staged external triggers. As a proof-of-concept, this platform is implemented as a gastrointestinal-retentive hydrogel gripper for localized intestinal enzyme delivery, where it exhibits thermally triggered gripping, millinewton-scale gripping force, autonomous reopening, and robust ex vivo retention on porcine small intestine under dynamic motion. These findings establish enzyme-programmed mechanical feedback as a general design strategy for self-regulated soft actuators and therapeutic materials with built-in functional lifetimes.

bioengineering↗

bioRxiv2026

Genetically Programmed Shape-morphing of Engineered Living Materials

Engineered living materials (ELMs) promise genetically programmable functions by coupling biological regulation to synthetic material responses. Here, we introduce genetically encoded, reversible shape-morphing in a peptide-crosslinked polyethylene glycol (PEG) hydrogel whose network density is modulated by opposing enzymatic pairs that induce crosslinking or hydrolysis. This molecular programmability alternates the hydrogel between deswelling and swelling/disintegration and produces 2 - 5-fold changes in mechanical properties. By fabricating a bilayer hydrogel with an inert layer, these molecular modulations are translated into a reversible and directional motion with angular bending motions exceeding 80{degrees}. Further, by embedding genetically engineered bacteria or interfacing mammalian cells, producing the relevant enzymatic cues, the reversible shape-morphing of these ELMs is programmed at the genetic level. We further demonstrate genetically programmed, autonomous reversible bending in a bilayer hydrogel controlled by out-of-equilibrium counteracting biochemical reactions with dynamically changing respective reaction rates. This work establishes a concept where coordinated polymer/peptide material engineering and synthetic biology yield autonomous shape-morphing ELMs, opening avenues toward biohybrid soft robotics, adaptive microfluidic systems, and dynamic biomedical interfaces.

synthetic biology↗

bioRxiv2019

Chemical unfolding of protein domains induces shape change in programmed protein hydrogels

Programmable behavior combined with tailored stiffness and tunable biomechanical response are key requirements for developing successful materials. However, these properties are still an elusive goal for protein-based biomaterials. Here, we present a new method based on protein-polymer interactions, to manipulate the stiffness of protein-based hydrogels made from bovine serum albumin (BSA) by using polyelectrolytes such as poly(Ethelene)imine (PEI) and poly-L-lysine (PLL) at various concentrations. This approach confers protein-hydrogels tunable wide-range stiffness, from ~ 10 - 60 kPa when treated with PEI, without affecting the protein mechanics and nanostructure. We ascribe the increase in stiffness to the synergistic effect of the non-covalent electrostatic polymer-protein interaction, as well as the polymer-shell that stabilizes the protein domains nanomechanics. We use the 6-fold increase in stiffness induced by PEI to program BSA-hydrogels in various shapes. By utilizing the characteristic protein unfolding we can induce reversible shape-memory behavior of these composite materials using chemical denaturing solutions. We anticipate this novel approach based on protein engineering and polymer reinforcing will enable the development and investigation of new smart biomaterials and extend protein hydrogel capabilities beyond their conventional applications.

biophysics↗