Click chemistry provides extremely selective and orthogonal reactions that proceed with high efficiency and under a variety of mild conditions, the most common example being the copper(I)-catalysed ...reaction of azides with alkynes. While the versatility of click reactions has been broadly exploited, a major limitation is the intrinsic toxicity of the synthetic schemes and the inability to translate these approaches into biological applications. This manuscript introduces a robust synthetic strategy where macromolecular precursors react through a copper-free click chemistry, allowing for the direct encapsulation of cells within click hydrogels for the first time. Subsequently, an orthogonal thiol-ene photocoupling chemistry is introduced that enables patterning of biological functionalities within the gel in real time and with micrometre-scale resolution. This material system enables us to tailor independently the biophysical and biochemical properties of the cell culture microenvironments in situ. This synthetic approach uniquely allows for the direct fabrication of biologically functionalized gels with ideal structures that can be photopatterned, and all in the presence of cells.
There has been enormous growth in faculty-led short-term study abroad programs because they offer flexibility and expand opportunities for students and faculty members who wish to study and work ...abroad but do not have the resources or time to spend a semester or year away. These experiential programs offer unique opportunities for university faculty to teach their disciplines abroad while engaging students in direct, authentic cultural encounters for transformative change.This volume provides a detailed framework and guidance on how to plan and implement a faculty-led study abroad program. Seasoned faculty leaders and administrators describe an overall program development process, comprehensively identify the elements for designing the curriculum, and offer advice and solutions to unique challenges inherent in various types of programs. The contributors cover the logistics for managing program details at home and abroad provide advice on writing a university proposal, creating a budget, the marketing and recruitment of students, handling abroad logistics, and preparing students for the abroad experience all illustrated by examples drawn from their experiences. Most importantly, readers will come to understand the difference between experiences that are more touristic than scholarly and gain guidance on designing or redesigning their own programs to ensure academically sound, culturally-relevant curricula that complements the international field site.The opening section sets the scene by describing the overall process of designing and delivering faculty-led abroad programs, from conception to implementation. The core of the book is grounded in evidence-based research for designing international curricula and syllabi, and includes five case studies illustrating short term programs focused on interdisciplinary subject matter, field study, global service learning, internship immersion, and language and cultural study. This practical guide concludes with faculty activities critical to a programs success: marketing and recruiting students; preparing teaching events for before, during, and after the abroad experience; and formulating a plan to leave a small footprint abroad. This book constitutes a handbook for college and university professors who plan to or already conduct short-term study abroad programs as well as administrators and staff of global and international programs.
To provide insight into how cells receive information from their external surroundings, synthetic hydrogels have emerged as systems for assaying cell function in well-defined microenvironments where ...single cues can be introduced and subsequent effects individually elucidated. However, as answers to more complex biological questions continue to be sought, advanced material systems are needed that allow dynamic alteration of the three-dimensional cellular environment with orthogonal reactions that enable multiple levels of control of biochemical and biomechanical signals. Here, we seek to synthesize one such three-dimensional culture system using cytocompatible and wavelength-specific photochemical reactions to create hydrogels that allow orthogonal and dynamic control of material properties through independent spatiotemporally regulated photocleavage of crosslinks and photoconjugation of pendant functionalities. The results demonstrate the versatile nature of the chemistry to create programmable niches to study and direct cell function by modifying the local hydrogel environment.
Stimuli-responsive materials undergo triggered changes when presented with specific environmental cues. These dynamic systems can leverage biological signals found locally within the body as well as ...exogenous cues administered with spatiotemporal control, providing powerful opportunities in next-generation diagnostics and personalized medicine. Here, we review the synthetic and strategic advances used to impart diverse responsiveness to a wide variety of biomaterials. Categorizing systems on the basis of material type, number of inputs, and response mechanism, we examine past and ongoing efforts toward endowing biomaterials with customizable sensitivity. We draw an analogy to computer science, whereby a stimuli-responsive biomaterial transduces a set of inputs into a functional output as governed by a user-specified logical operator. We discuss Boolean and non-Boolean operations, as well as the various chemical and physical modes of signal transduction. Finally, we examine current limitations and promising directions in the ongoing development of programmable stimuli-responsive biomaterials.
A photodegradable material‐based approach to generate endothelialized 3D vascular networks within cell‐laden hydrogel biomaterials is introduced. Exploiting multiphoton lithography, microchannel ...networks spanning nearly all size scales of native human vasculature are readily generated with unprecedented user‐defined 4D control. Intraluminal channel architectures of synthetic vessels are fully customizable, providing new opportunities for next‐generation microfluidics and directed cell function.
A photodegradable material‐based approach to generate endothelialized 3D vascular networks within cell‐laden hydrogel biomaterials is introduced. Exploiting multiphoton lithography, microchannel networks spanning size scales of nearly all native human vasculature are readily generated with unprecedented user‐defined 4D control. Intraluminal channel architectures of synthetic vessels are fully customizable, providing new opportunities for next‐generation microfluidics and directed cell function.
Lysine (Lys) residues in proteins undergo a wide range of reversible post-translational modifications (PTMs), which can regulate enzyme activities, chromatin structure, protein-protein interactions, ...protein stability, and cellular localization. Here we discuss the “writers,” “erasers,” and “readers” of some of the common protein Lys PTMs and summarize examples of their major biological impacts. We also review chemical biology approaches, from small-molecule probes to protein chemistry technologies, that have helped to delineate Lys PTM functions and show promise for a diverse set of biomedical applications.
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Zhipeng Wang and Philip Cole review major types of chemical modifications of the amino acid lysine in proteins and how they are added and removed. They also discuss a number of chemical approaches and how they have been applied to clarify the roles of lysine modifications in biology and medicine.
Photoresponsive materials have been widely used in vitro for controlled therapeutic delivery and to direct 4D cell fate. Extension of the approaches into a bodily setting requires use of low‐energy, ...long‐wavelength light that penetrates deeper into and through complex tissue. This review details recent reports of photoactive small molecules and proteins that absorb visible and/or near‐infrared light, opening the door to exciting new applications in multiplexed and in vivo regulation.
Light‐responsive materials have made waves on the benchtop, facilitating cutting‐edge research with incredible potential. However, nearly all efforts to translate these new materials into clinical applications have been thwarted by the limitations of light's poor penetration depth in living tissue. This review highlights new biomaterials that respond to lower energy light with better penetration for expanded in vivo applications.
Photodynamic hydrogel biomaterials have demonstrated great potential for user-triggered therapeutic release, patterned organoid development, and four-dimensional control over advanced cell fates in ...vitro. Current photosensitive materials are constrained by their reliance on high-energy ultraviolet light (<400 nm) that offers poor tissue penetrance and limits access to the broader visible spectrum. Here, we report a family of three photolabile material crosslinkers that respond rapidly and with unique tricolor wavelength-selectivity to low-energy visible light (400-617 nm). We show that when mixed with multifunctional poly(ethylene glycol) macromolecular precursors, ruthenium polypyridyl- and ortho-nitrobenzyl (oNB)-based crosslinkers yield cytocompatible biomaterials that can undergo spatiotemporally patterned, uniform bulk softening, and multiplexed degradation several centimeters deep through complex tissue. We demonstrate that encapsulated living cells within these photoresponsive gels show high viability and can be successfully recovered from the hydrogels following photodegradation. Moving forward, we anticipate that these advanced material platforms will enable new studies in 3D mechanobiology, controlled drug delivery, and next-generation tissue engineering applications.
We present results from the largest Ca ii triplet line metallicity study of Small Magellanic Cloud (SMC) field red giant stars to date, involving 3037 objects spread across approximately 37.5 deg2, ...centred on this galaxy. We find a median metallicity of Fe/H = −0.99 ± 0.01, with clear evidence for an abundance gradient of −0.075 ± 0.011 dex deg−1 over the inner 5°. We interpret the abundance gradient to be the result of an increasing fraction of young stars with decreasing galactocentric radius, coupled with a uniform global age–metallicity relation. We also demonstrate that the age–metallicity relation for an intermediate-age population located 10 kpc in front of the north-east of the cloud is indistinguishable from that of the main body of the galaxy, supporting a prior conjecture that this is a stellar analogue of the Magellanic Bridge. The metal-poor and metal-rich quartiles of our red giant branch star sample (with complementary optical photometry from the Magellanic Clouds Photometric Survey) are predominantly older and younger than approximately 6 Gyr, respectively. Consequently, we draw a link between a kinematical signature, tentatively associated by us with a disc-like structure, and the upsurges in stellar genesis imprinted on the star formation history of the central regions of the SMC. We conclude that the increase in the star formation rate around 5–6 Gyr ago was most likely triggered by an interaction between the SMC and Large Magellanic Cloud.
The successful transport of drug- and cell-based therapeutics to diseased sites represents a major barrier in the development of clinical therapies. Targeted delivery can be mediated through ...degradable biomaterial vehicles that utilize disease biomarkers to trigger payload release. Here, we report a modular chemical framework for imparting hydrogels with precise degradative responsiveness by using multiple environmental cues to trigger reactions that operate user-programmable Boolean logic. By specifying the molecular architecture and connectivity of orthogonal stimuli-labile moieties within material cross-linkers, we show selective control over gel dissolution and therapeutic delivery. To illustrate the versatility of this methodology, we synthesized 17 distinct stimuli-responsive materials that collectively yielded all possible YES/OR/AND logic outputs from input combinations involving enzyme, reductant and light. Using these hydrogels we demonstrate the first sequential and environmentally stimulated release of multiple cell lines in well-defined combinations from a material. We expect these platforms will find utility in several diverse fields including drug delivery, diagnostics and regenerative medicine.
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