Select search scope: search across all journals or within the current journal
Restricted accessIntroductionFirst published March, 2019pp. 281-282
Open accessResearch articleFirst published March, 2019pp. 283-293Nanomedicines for controlled drug release provide temporal and spatial regulation of drug bioavailability in the body. The timing of drug release is usually engineered either for slow gradual release over an extended period of time or for rapid release triggered by a specific change in its physicochemical environment. However, between these two extremes, there is the desirable possibility of adaptive nanomedicines that dynamically modulate drug release in tune with its changing environment. Adaptation and response through communication with its environment is a fundamental trait of living systems; therefore, the design of biomimetic nanomedicines through the approaches of bottom-up synthetic biology provides a viable route to this goal. This could enable drug delivery systems to optimize release in synchronicity with the body’s natural biological rhythms and the personalized physiological characteristics of the patient, e.g. their metabolic rate. Living systems achieve this responsiveness through feedback-controlled biochemical processes that regulate their functional outputs. Towards this goal of adaptive drug delivery systems, we review the general benefits of nanomedicine formulations, provide existing examples of experimental nanomedicines that encapsulate the metabolic function of enzymes, and give relevant examples of feedback-controlled chemical systems. These are the underpinning concepts that hold promise to be combined to form novel adaptive release systems. Furthermore, we motivate the advantages of adaptive release through chronobiological examples. By providing a brief review of these topics and an assessment of the state of the art, we aim to provide a useful resource to accelerate developments in this field.
The timing and rate of release of pharmaceuticals from advanced drug delivery systems is an important property that has received considerable attention in the scientific literature. Broadly, these mostly fall into two classes: controlled release with a prolonged release rate or triggered release where the drug is rapidly released in response to an environmental stimulus. This review aims to highlight the potential for developing adaptive release systems that more subtlety modulate the drug release profile through continuous communication with its environment facilitated through feedback control. By reviewing the key elements of this approach in one place (fundamental principles of nanomedicine, enzymatic nanoreactors for medical therapies and feedback-controlled chemical systems) and providing additional motivating case studies in the context of chronobiology, we hope to inspire innovative development of novel “chrononanomedicines.”
Restricted accessReview articleFirst published March, 2019pp. 294-303Phospholipid membranes are necessary for the compartmentalization of chemistries within biological cells and for initiation and propagation of cell signaling. The morphological and chemical complexities of cellular membranes represent a challenge for dissecting the biochemical processes occurring at these interfaces. Therefore, investigations of the biological events occurring at the membrane require suitable models to reproduce the intricacy of this surface. Solid-supported lipid bilayers (SLBs) are simplified physical replicas of biological membranes that allow for bottom-up reconstruction of the molecular mechanisms occurring at cellular interfaces. In this brief review, we introduce how the properties of SLBs can be tuned to mimic biological membranes, highlighting the engineering approaches for creating spatially resolved patterns of lipid bilayers and supported membranes with curved geometries. Additionally, we present how SLBs have been employed to reconstitute molecular mechanisms involved in intercellular signaling and more recently, membrane trafficking.
Artificial membranes with complex topography aid the understanding of biological processes where membrane geometry plays a key regulatory role. In this review, we highlight how emerging material and engineering technologies have been employed to create minimal models of cell signaling pathways,
Open accessResearch articleFirst published March, 2019pp. 304-313
The traditional route to investigating biology by perturbing living systems or by individually purifying and characterizing component parts is giving way to more complex endeavors where chemists and physicists attempt to build cells from scratch. Parallel efforts are underway that either exploits extant biological parts or prebiotically plausible molecules. Both approaches help to reveal the underlying physical–chemical forces that give rise to cellular function and highlight the important role played by polymers in regulating biological chemical systems. Although the success in RNA and lipid chemistry has led to the reconstitution of specific facets of cellular life, our understanding of dynamic, dissipative networks is currently too incomplete to allow for the construction of a self-sustained, integrated protocell. However, the presence of shared chemistry points to a promising path forward.
Advances in the understanding of the biophysics of membranes, the nonenzymatic and enzymatic polymerization of RNA, and in the design of complex chemical reaction networks have led to a new, integrated way of viewing the shared chemistry needed to sustain life. Although a protocell capable of Darwinian evolution has yet to be built, the seemingly disparate pieces are beginning to fit together. At the very least, better cellular mimics are on the horizon that will likely teach us much about the physicochemical underpinnings of cellular life.
Restricted accessResearch articleFirst published March, 2019pp. 314-322In situ generation of proton gradients across membranes is a key component for energy generation within cells and is therefore an important feature for the design of energy converting artificial cells. Here, we establish a stepwise method for the
Our results offer the potential for straightforward, additive-free, and molecularly simple routes to building complex bioreactors based on
Open accessResearch articleFirst published March, 2019pp. 323-331Population growth, climate change, and dwindling finite resources are amongst the major challenges which are facing the planet. Requirements for food, materials, water, and energy will soon exceed capacity. Green biotechnology, fueled by recent plant synthetic biology breakthroughs, may offer solutions. This review summarizes current progress towards robust and predictable engineering of plants. I then discuss applications from the lab and field, with a focus on bioenergy, biomaterials, and medicine.
The plant synthetic biology field has exploded in the last five years, in part driven by techniques such as CRISPR and cheap DNA synthesis. This review summarizes the current state of research in plant synthetic biology, and how it is being applied to two topics: renewable fuels and chemicals, and medicine.