Hydrogels for tissue engineering.

New generations of synthetic biomaterials are being developed at a rapid pace for use as three-dimensional extracellular microenvironments to mimic the regulatory characteristics of natural extracellular matrices (ECMs) and ECM-bound growth factors, both for therapeutic applications and basic biological studies. Recent advances include nanofibrillar networks formed by self-assembly of small building blocks, artificial ECM networks from protein polymers or peptide-conjugated synthetic polymers that present bioactive ligands and respond to cell-secreted signals to enable proteolytic remodeling. These materials have already found application in differentiating stem cells into neurons, repairing bone and inducing angiogenesis. Although modern synthetic biomaterials represent oversimplified mimics of natural ECMs lacking the essential natural temporal and spatial complexity, a growing symbiosis of materials engineering and cell biology may ultimately result in synthetic materials that contain the necessary signals to recapitulate developmental processes in tissue- and organ-specific differentiation and morphogenesis.

https://sisu.ut.ee/sites/default/files/quantum/files/synthetic_biomaterials_as_instructive_extracellular_microenvironments_for_morphogenesis_in_tissue_engineering_lutolf_m.p_hubbell_j.a_2005_0.pdf

Synthetic biomaterials as instructive extracellular microenvironments for morphogenesis in tissue engineering

Biomaterials have played an enormous role in the success of medical devices and drug delivery systems. We discuss here new challenges and directions in biomaterials research. These include synthetic replacements for biological tissues, designing materials for specific medical applications, and materials for new applications such as diagnostics and array technologies.

Designing materials for biology and medicine

Thermo- and pH-responsive polymers in drug delivery.

RGD modified polymers: biomaterials for stimulated cell adhesion and beyond

This article, on protein-based polymers comprised of repeating peptide sequences, reviews studies from the author's laboratory covering a period of more than two decades; it presents a general mechanism for protein folding and function and demonstrates the mechanism by designing model proteins capable of performing many of the energy conversions that sustain life and by designing diverse biomolecular machines and materials with promising applications for society. All polymers with the correct balance of apolar and polar moieties, including water soluble proteins and protein-based polymers, increase order by a hydrophobic folding and assembly transition as the temperature is raised above a critical onset temperature, designated as Tt. Instead of varying the temperature, however, innumerable variables lower the value of Tt from above to below the operating temperature to drive folding and function. Thus, this inverse temperature transition provides a fundamental mechanism whereby proteins fold and function ...

Physical Chemistry of Biological Free Energy Transduction As Demonstrated by Elastic Protein-Based Polymers†

Numerous physical characterizations clearly demonstrate that the polypentapeptide of elastin (Val1-Pro2-Gly3-Val4-Gly5)n in water undergoes an inverse temperature transition. Increase in order occurs both intermolecularly and intramolecularly on raising the temperature from 20 to 40 degrees C. The physical characterizations used to demonstrate the inverse temperature transition include microscopy, light scattering, circular dichroism, the nuclear Overhauser effect, temperature dependence of composition, nuclear magnetic resonance (NMR) relaxation, dielectric relaxation, and temperature dependence of elastomer length. At fixed extension of the cross-linked polypentapeptide elastomer, the development of elastomeric force is seen to correlate with increase in intramolecular order, that is, with the inverse temperature transition. Reversible thermal denaturation of the ordered polypentapeptide is observed with composition and circular dichroism studies, and thermal denaturation of the crosslinked elastomer is also observed with loss of elastomeric force and elastic modulus. Thus, elastomeric force is lost when the polypeptide chains are randomized due to heating at high temperature. Clearly, elastomeric force is due to nonrandom polypeptide structure. In spite of this, elastomeric force is demonstrated to be dominantly entropic in origin. The source of the entropic elastomeric force is demonstrated to be the result of internal chain dynamics, and the mechanism is called the librational entropy mechanism of elasticity. There is significant application to the finding that elastomeric force develops due to an inverse temperature transition. By changing the hydrophobicity of the polypeptide, the temperature range for the inverse temperature transition can be changed in a predictable way, and the temperature range for the development of elastomeric force follows. Thus, elastomers have been prepared where the development of elastomeric force is shifted over a 40 degrees C temperature range from a midpoint temperature of 30 degrees C for the polypentapeptide to 10 degrees C by increasing hydrophobicity with addition of a single CH2 moiety per pentamer and to 50 degrees C by decreasing hydrophobicity.(ABSTRACT TRUNCATED AT 400 WORDS)

/pdf/entropic-elastic-processes-in-protein-mechanisms-i-elastic-6uj6d0m4y1.pdf

Entropic elastic processes in protein mechanisms. I. Elastic structure due to an inverse temperature transition and elasticity due to internal chain dynamics.

Certain model proteins dramatically fold and become more ordered on raising the temperature. When the temperature is raised to drive folding and assembly, these model proteins can lift weights and perform work; they can produce motion. The temperature of warm-blooded animals, however, is kept constant. Therefore, motion cannot result from a change in temperature. In this case, a free energy change, caused, for example, by an increase in the concentration of a chemical, can lower the temperature at which the protein folding and assembly transition occurs from above to below physiological temperature. Raising the concentration of a chemical isothermally has indeed been shown to result in motion and the efficient performance of work. These model proteins and the mechanism they reveal provide insight into the molecular basis for diverse biological functions; they are models for the molecular machines that comprise the living organism, and they provide a new class of materials for both medical and nonmedical applications.

Molecular Machines: How Motion and Other Functions of Living Organisms Can Result from Reversible Chemical Changes

Temperature of polypeptide inverse temperature transition depends on mean residue hydrophobicity

Biologicalfree energy transduction: Living organisms evolved by developing the capacity to utilize energy in one form and to convert it into energy of different forms. How can the principal players in such processes, the proteins and their constituent polypeptides, function in the conversion of one form of energy into another? The set of pairwise free energy transductions, other than photon-driven processes, that can occur in biological systems involve the intensive variables of temperature, pressure, mechanical force, chemical potential and electrochemical potential (see below). What is (or what are) the primary mechanism (or mechanisms) whereby these couplings or transductions can occur? Is it possible that there could be a common mechanism for these seemingly diverse interconversions ranging from the more obvious chemomechanical transduction of muscle contraction to the free energy transductions involved in oxidative phosphorylation?

Dan W. Urry

Papers

Physical Chemistry of Biological Free Energy Transduction As Demonstrated by Elastic Protein-Based Polymers†

Entropic elastic processes in protein mechanisms. I. Elastic structure due to an inverse temperature transition and elasticity due to internal chain dynamics.

Molecular Machines: How Motion and Other Functions of Living Organisms Can Result from Reversible Chemical Changes

Temperature of polypeptide inverse temperature transition depends on mean residue hydrophobicity

Free energy transduction in polypeptides and proteins based on inverse temperature transitions.