抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

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

https://imechanica.org/files/Qiu_environmental_sensitive_hydrogel.pdf

Environment-sensitive hydrogels for drug delivery

Hydrophilic polymers are the center of research emphasis in nanotechnology because of their perceived “intelligence”. They can be used as thin films, scaffolds, or nanoparticles in a wide range of biomedical and biological applications. Here we highlight recent developments in engineering uncrosslinked and crosslinked hydrophilic polymers for these applications. Natural, biohybrid, and synthetic hydrophilic polymers and hydrogels are analyzed and their thermodynamic responses are discussed. In addition, examples of the use of hydrogels for various therapeutic applications are given. We show how such systems’ intelligent behavior can be used in sensors, microarrays, and imaging. Finally, we outline challenges for the future in integrating hydrogels into biomedical applications.

/pdf/hydrogels-in-biology-and-medicine-from-molecular-principles-3lowrzjjsl.pdf

Hydrogels in Biology and Medicine: From Molecular Principles to Bionanotechnology†

Stimuli-sensitive polymer hydrogels, which swell or shrink in response to changes in the environmental conditions, have been extensively investigated and used as 'smart' biomaterials and drug-delivery systems Most of these responsive hydrogels are prepared from a limited number of synthetic polymers and their derivatives, such as copolymers of (meth)acrylic acid, acrylamide and N-isopropyl acrylamide Water-soluble synthetic polymers have also been crosslinked with molecules of biological origin, such as oligopeptides and oligodeoxyribonucleotides, or with intact native proteins Very often there are several factors influencing the relationship between structure and properties in these systems, making it difficult to engineer hydrogels with specified responses to particular stimuli Here we report a hybrid hydrogel system assembled from water-soluble synthetic polymers and a well-defined protein-folding motif, the coiled coil These hydrogels undergo temperature-induced collapse owing to the cooperative conformational transition of the coiled-coil protein domain This system shows that well-characterized water-soluble synthetic polymers can be combined with well-defined folding motifs of proteins in hydrogels with engineered volume-change properties

Hybrid hydrogels assembled from synthetic polymers and coiled-coil protein domains

https://www.cell.com/cell/pdf/0092-8674(90)90412-8.pdf

The kinesin-like ncd protein of Drosophila is a minus end-directed microtubule motor

The challenges of developing medical adhesives for the wet environment of open surgery are analogous to the adhesion problems solved by marine organisms living at the watery interface of land and ocean. These organisms routinely bond dissimilar materials together under seawater with little if any surface preparation. One such organism is the sandcastle worm (Phragmatopoma californica). Our goal is to copy this marine worm’s mechanisms of underwater bonding to create synthetic water-borne underwater medical adhesives, and in turn, to use the synthetic adhesives to test mechanistic hypotheses about the natural adhesive. Biomimetic underwater adhesives were formulated with polyelectrolytic analogues of the natural glue proteins. The copolymers condensed into complex coacervates—dense partially water-immiscible cohesive fluids poised between soluble polymers and insoluble polymeric salts. The boundary between fluid coacervate phases and solid or gelled states was dependent on divalent cation species as well as the pH and temperature, which demonstrated that these environmental factors can trigger the adhesive setting reaction (Fig. 1). The results provide, respectively, empirical support for the natural pH-triggered set hypothesis and practical triggers for controlled setting of mimetic medical adhesives.

/pdf/biomimetic-underwater-adhesives-with-environmentally-2u24gibr35.pdf

Biomimetic Underwater Adhesives with Environmentally Triggered Setting Mechanisms

The general topic of this review is protein-based underwater adhesives produced by aquatic organisms. The focus is on mechanisms of interfacial adhesion to native surfaces and controlled underwater solidification of natural water-borne adhesives. Four genera that exemplify the broad range of function, general mechanistic features, and unique adaptations are discussed in detail: blue mussels, acorn barnacles, sandcastle worms, and freshwater caddisfly larva. Aquatic surfaces in nature are charged and in equilibrium with their environment, populated by an electrical double layer of ions as well as adsorbed natural polyelectrolytes and microbial biofilms. Surface adsorption of underwater bioadhesives likely occurs by exchange of surface bound ligands by amino acid sidechains, driven primarily by relative affinities and effective concentrations of polymeric functional groups. Most aquatic organisms exploit modified amino acid sidechains, in particular phosphorylated serines and hydroxylated tyrosines (dopa), with high-surface affinity that form coordinative surface complexes. After delivery to the surfaces as a fluid, permanent natural adhesives solidify to bear sustained loads. Mussel plaques are assembled in a manner superficially reminiscent of in vitro layer-by-layer strategies, with sequentially delivered layers associated through Fe(dopa)(3) coordination bonds. The adhesives of sandcastle worms, caddisfly larva, and barnacles may be delivered in a form somewhat similar to in vitro complex coacervation. Marine adhesives are secreted, or excreted, into seawater that has a significantly higher pH and ionic strength than the internal environment. Empirical evidence suggests these environment triggers could provide minimalistic, fail-safe timing mechanisms to prevent premature solidification (insolubilization) of the glue within the secretory system, yet allow rapid solidification after secretion. Underwater bioadhesives are further strengthened by secondary covalent curing.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/polb.22256

Russell J. Stewart

Papers

Hybrid hydrogels assembled from synthetic polymers and coiled-coil protein domains

The kinesin-like ncd protein of Drosophila is a minus end-directed microtubule motor

Biomimetic Underwater Adhesives with Environmentally Triggered Setting Mechanisms

Natural Underwater Adhesives

Cement proteins of the tube-building polychaete Phragmatopoma californica.