Protocells自由边界生长模型的适定性

研究模拟protocells生长的自由边界问题,此问题中控制自由边界Ω(t)移动的演化方程为Vn=-v n-βv,其中Vn表示边界Ω(t)的法向速度,v为构造物质的密度,β为正常数。在1999年,Cu i和Friedm an已研究了此问题径向对称的情况。主要针对径向不对称的情况。利用Banach空间中抛物方程的抽象理论证明此问题在little H lder空间是局部适定的。

左旋多巴和姜黄素共递送protocells纳米粒的制备及体外评价

目的制备共载左旋多巴和姜黄素protocells纳米粒并进行体外评价。方法以介孔二氧化硅为内核,脂质双分子层为外膜,制备共载左旋多巴和姜黄素protocells纳米粒。使用激光粒度分析仪和透射电子显微镜对所制备纳米粒的形貌、粒径、多分散系数(PDI)和Zeta电势进行表征;采用高效液相色谱法对所制备纳米粒的载药量和包封率进行测定;采用透析袋法对所制备纳米粒的体外释放特性进行考察;应用粒径、Zeta电势、载药量等指标对所制备纳米粒的室温贮存稳定性进行评价。结果制备的载左旋多巴和姜黄素protocells纳米粒粒径分布均一性好、粒子表面呈电负性、平均粒径为(210.9±2.8)nm、PDI为(0.201±0.011)。其中左旋多巴的载药量为(20.28±0.43)%、包封率为(10.14±0.22)%;姜黄素的载药量为(1.97±0.01)%、包封率为(98.32±0.01)%。体外释放结果表明该纳米粒48 h姜黄素累计释放率为59.2%,且可有效阻止左旋多巴的泄漏,降低其在循环系统中的暴露量。稳定性结果表明左旋多巴和姜黄素在protocells纳米粒中稳定性良好。结论载左旋多巴和姜黄素的protocells纳米粒制备工艺简单,具有良好的理化性质、稳定性及所预期的释放性能。

Theoretical perspective on synthetic man-made life:Learning from the origin of life

Creating a man-made life in the laboratory is one of life science's most intriguing yet challenging problems.Advances in synthetic biology and related theories,particularly those related to the origin of life,have laid the groundwork for further exploration and understanding in this field of artificial life or man-made life.But there remains a wealth of quantitative mathematical models and tools that have yet to be applied to this area.In this paper,we review the two main approaches often employed in the field of man-made life:the top-down approach that reduces the complexity of extant and existing living systems and the bottom-up approach that integrates welldefined components,by introducing the theoretical basis,recent advances,and their limitations.We then argue for another possible approach,namely"bottom-up from the origin of life":Starting with the establishment of autocatalytic chemical reaction networks that employ physical boundaries as the initial compartments,then designing directed evolutionary systems,with the expectation that independent compartments will eventually emerge so that the system becomes free-living.This approach is actually analogous to the process of how life originated.With this paper,we aim to stimulate the interest of synthetic biologists and experimentalists to consider a more theoretical perspective,and to promote the communication between the origin of life community and the synthetic man-made life community.

Feasible Fabrication of Hollow Micro-vesicles by Non-amphiphilic Macromolecules Based on Interfacial Cononsolvency

Herein we present a new perspective showing that water-soluble liquids,when added to water,undergo transient emulsification before complete dissolution.Thus,non-amphiphilic macromolecules can self-assemble at the two-miscible-phase interface when cononsolvent effect appears.A representative case shown here is that when poly(A/-isopropylacrylamide)(PNIPAm),prepared by aqueous radical polymerization,in methanol solution is added into water,the polymer chains rapidly self-assemble into hollow micro-vesicles based on the cononsolvency at water/methanol interface.This finding provides a subtle strategy to prepare hollow micro-vesicles by non-amphiphilic polymers without template participating.We proposed a new concept^interfacial cononsolvencyw to describe the formation process.Due to the easy modification process,sugar-contained PNIPAm chains are synthesized by copolymerization.As an application example,it is shown that these sugar-contained PNIPAm chains can afford MsweetH micro-vesicles(containing glucose residues).And the"sweer"micro-vesicles can well mimick the protocells which are involved in the recognition of bacteria.

Regulating FUS Liquid-Liquid Phase Separation via Specific Metal Recognition

Liquid-liquid phase separation(LLPS)or biomolecular condensation that leads to formation of membraneless organelles plays a critical role in many biochemical processes.Mechanism study of regulating LLPS is therefore central to the understanding of protein aggregation and disease-relevant process.We report a fused in sarcoma protein(FUS)-derived low complexity(LC)sequence that undergoes LLPS in the presence of metal ions.The LC protein was constructed by fusing a hexhistidine-tag to the N-terminal low complexity domain(the residues 1–165 in QGSY-rich segment)of FUS.Spontaneous condensation of the intrinsic disordered protein into coacervate droplets was observed in the presence of metal ions that chelate oligohistidine moieties to form protein matrix.We demonstrate the key role of metal ion-histidine coordination in governing LLPS behaviours and the fluidity of biomolecular condensates.By taking advantage of competitive binding using chelators,we show the possibility of regulating dynamic behaviors of disease-relevant protein droplets,and developing a potential approach towards controllable biological encapsulation/release.

Pearling and helical nanostructures of model protocell membranes

The diversity of protocell membrane structures is crucial for the regulation of cell activities and indispensable to the origin of life.Prior to the evolution of complex cellular machinery,spontaneous protocell membrane evolution results from the intrinsic physicochemical properties of simple molecules under specific environmental conditions.Here,we report the evolution of the morphology of cell-sized model protocell membranes from giant vesicles to pearling and helical nanostructures,resembling morphologies of eukaryocytes,nostoc,and spirilla.This evolution occurs in a single binary aqueous system composed of an achiral single-chain amphiphile and a biogenic polyamine(spermidine or spermine)upon evaporating water,feeding amphiphiles,or increasing pH in response to various primitive fluctuating conditions.In contrast,nonbiogenic polyamines(triamine,triethylenetetramine,and hexamethyltriethylenetetramine)with slight differences in the number of methylene groups or protonated amine groups do not induce such a kind of evolution.The evolution of the shape transformation strongly relies on the balance between electrostatic attraction and hydrogen bonding,attributed to the odd/even effect of polyamines in the assembly.Strikingly,both pearling and helical structures emerge from multilamellar vesicles undergoing different processes,where the helix shows stronger permeability and encapsulation capability due to its multicompartmentalized structure.Thus,subtle adjustment of weak intramolecular interactions not only yields significant changes in the morphological evolution of protocell membranes but also brings new insights into the natural inevitability of biogenic small molecules.