Cell‐Inspired All‐Aqueous Microfluidics: From Intracellular Liquid–Liquid Phase Separation toward Advanced Biomaterials

Ma, Qingming; Song, Yang; Sun, Wentao; Cao, Jie; Yuan, Hao; Wang, Xinyu; Sun, Yong; Shum, Ho Cheung

doi:10.1002/advs.201903359

Cited by 138 publications

(95 citation statements)

References 268 publications

(478 reference statements)

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“…[210,211] For instance, polyelectrolytes, such as polypeptides, nucleotides and polysaccharides, can phase separate driven by electrostatic interactions; [212] nonpolar macromolecular polymers and salts also can phase separate. [31,32,63] The phase separation between positively charged and negatively charged molecules leads to coacervate droplets or solid precipitates, depending on the molecular weight, concentration and charge density of molecules. [213][214][215] Coacervate droplets refer to spontaneously formed polymerrich droplets inside a polymer-depleted phase (Figure 7a).…”

Section: Membraneless Coacervated Dropletsmentioning

confidence: 99%

“…[52] This is different from aqueous two-phase systems (ATPS), where two phases enriched in different polymers are formed (Figure 7b). [31,32,216,217] Coacervate droplets are biological relevant since they provide highly crowded compartments, which not only segregate biochemical reactions, but also enrich precursors and enzymes to support remarkably high reaction rate, for instance, the transcription and translation rate of mRNA. [52,185,[218][219][220] Thus, coacervate droplets formed by interactions between anionic nucleotides/polynucleotides and cationic peptides/polypeptides, are useful platforms for exploring the protocell evolution and understanding intracellular machinery of membraneless organelles.…”

Section: Membraneless Coacervated Dropletsmentioning

confidence: 99%

“…[62] In addition, the recent discovery of macromolecule crowding in living cells may contribute to the high efficiency of intracellular/ subcellular enzymatic reactions, thus stimulating enormous interests of coacervate droplets. [31][32][33][34][35][36][37][63][64][65][66][67][68][69] Moreover, the development in cell-inspired novel carriers for therapeutic nuclei acids and proteins has been progressed excitingly with translational successes. For a prosperous and interdisciplinary field like synthetic cells, there are reviews summarizing from specific aspects, for instance, tailoring appearance of synthetic cells, [2,[70][71][72] elucidating specific functions of synthetic cell modules, [2,71,73] which include adhesion, [58] growth, [57] energy regeneration/conversion, [4,[59][60][61] gene circuits, [56,74] and cellular interactions, [75][76][77] exclusively focusing on applications of synthetic compartments such as delivery carriers [10,18,[78][79][80][81][82][83][84][85]…”

Section: Introductionmentioning

confidence: 99%

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Interface Engineering in Multiphase Systems toward Synthetic Cells and Organelles: From Soft Matter Fundamentals to Biomedical Applications

et al. 2020

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products of evolution over billions of years. They are featured by multiple hierarchical compartments performing specialized and exquisitely coordinated functions. The biological and genetic complexity of cells and subcellular components make understanding their physicochemical foundation piece by piece challenging. [1-5] Moreover, the mystery of how the very first cell, protocell, comes into exist in early earth scenario is unveiled yet. [6] Motivated by understanding protocell and biological cells, synthetic cells are being constructed. Started form the simplest form, aqueous droplet enclosed by a bilayer structure, researchers adopt a bottom-up approach to study machineries of biological cells, and explore possible forms of the protocell in early world conditions. [7] Synthetic cells are important to bridge the gap between cellular organism and nonliving matter. They refer to synthetic compartments that encapsulate a wide variety of molecules and mimic one or multiple cellular functions. By segregation of contents in different compartments, synthetic cells are now engineered to perform multiple processes and functions, including segregating genetic information, genetic circuits, protein synthesis, metabolism, growth, reproduce, recognition, intercellular crosstalk, and adaptivity to surroundings. [8-17] In these simplified cell models, cellular processes and signal pathways are reconstituted, providing insights for cell biology and offering new opportunities for designing smart cell-like carriers of therapeutics. [18-26] In addition, the hypothesis of "RNA world" has inspired the investigation of synthetic compartments as protocells, in which nucleotide permeation, compartmental division, the synthesis of macromolecular polynucleotide, and the polymerization of ribonucleic acids (RNA) are explored. [7,27,28] The beginning of synthesizing cell-like structures starts from amphiphiles self-assembled at liquid/liquid interfaces to form enclosed compartments. [29-32] Recently, techniques such as microfluidics facilitate the fabrication of complex compartments with high-order hierarchy with excellent control. [33-36] Formulations of compartmentalization can be diverse, there are reviews mainly focused on one particular type of synthetic compartments, such as lipid vesicles (liposomes), [22,30,37,38] polymer vesicles (polymersomes), [39-43] lipid-polymer hybrid Synthetic cells have a major role in gaining insight into the complex biological processes of living cells; they also give rise to a range of emerging applications from gene delivery to enzymatic nanoreactors. Living cells rely on compartmentalization to orchestrate reaction networks for specialized and coordinated functions. Principally, the compartmentalization has been an essential engineering theme in constructing cell-mimicking systems. Here, efforts to engineer liquid-liquid interfaces of multiphase systems into membrane-bounded and membraneless compartments, which include lipid vesicles, polymer vesicles, colloidosomes, hybrids, and coacervate droplets,...

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Section: Membraneless Coacervated Dropletsmentioning

confidence: 99%

Section: Membraneless Coacervated Dropletsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Interface Engineering in Multiphase Systems toward Synthetic Cells and Organelles: From Soft Matter Fundamentals to Biomedical Applications

et al. 2020

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“…In recent years, cell-mediated DDS has become a promising strategy to address the above challenges (Ma, Song, et al, 2020;Shen et al, 2020). This novel strategy takes advantage of cellular unique properties, such as circulating in the bloodstream for a period of time, abundant surface ligands, targeting (cancer) cells, flexible morphology, through challenging biological barriers as well as cellular signaling and metabolism, to maximize therapeutic outcomes as well as minimize side effects (Su et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Cell-mediated targeting drugs delivery systems

Yang

et al. 2020

Drug Delivery

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Drug delivery systems have shown tremendous promise to improve the diagnostic and therapeutic effects of drugs due to their special property. Targeting tissue damage, tumors, or drugs with limited toxicity at the site of infection is the goal of successful pharmaceuticals. Targeted drug delivery has become significantly important in enhancing the pharmaceutical effects of drugs and reducing their side effects of therapeutics in the treatment of various disease conditions. Unfortunately, clinical translation of these targeted drug delivery system mechanisms faces many challenges. At present, only a few targeted drug delivery systems can achieve high targeting efficiency after intravenous injection, even though numerous surface markers and targeting approaches have been developed. Thus, cellmediated drug-delivery targeting systems have received considerable attention for their enhanced therapeutic specificity and efficacy in the treatment of the disease. This review highlights the recent advances in the design of the different types of cells that have been explored for cell-mediated drug delivery and targeting mechanisms. A better understanding of cell biology orientation and a new generation of delivery strategies that utilize these endogenous approaches are expected to provide better solutions for specific site delivery and further facilitate clinical translation.

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“…[36][37][38][39][40][41][42][43] Microfluidics is a science and technology that precisely controls and manipulates microscale fluids in micronanoscale spaces. [44][45][46][47][48][49][50] Therefore, microfluidic technology provides an advanced platform to accurately control the replacement of culture media, interconnect different types of tissue, and allow for rapid changes in culture conditions. Due to the precise control of microenvironmental parameters, microfluidic technology has a wide range of new cell culture applications, particularly in the field of 3D cell culture.…”

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confidence: 99%

Development of Cell Spheroids by Advanced Technologies

Shao

Chi

Zhang

et al. 2020

Adv Materials Technologies

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3D cell culture has been strongly advocated as a highly useful culture technique instead of the traditional 2D cell culture. Specially, spheroids, as the primary mode of 3D cell culture, allow cells to establish a connection between the cell and the extracellular matrix to form a specific 3D structure that better mimics the growing environment of cells in vivo. Benefiting from the emergence of various advanced micromachining platforms, spheroids have received increasing attention in diverse fields. Herein, the combination of the cell spheroid culture with microfluidic technology is reviewed. After concisely introducing the traditional methods for fabricating cell spheroids, an outline of the approaches for preparing cell spheroids using different advanced techniques is given. Then, the various applications of the generated cell spheroids in the field of biomedical engineering are presented and the current limitations, challenges, and future directions are summarized.

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Cell‐Inspired All‐Aqueous Microfluidics: From Intracellular Liquid–Liquid Phase Separation toward Advanced Biomaterials

Cited by 138 publications

References 268 publications

Interface Engineering in Multiphase Systems toward Synthetic Cells and Organelles: From Soft Matter Fundamentals to Biomedical Applications

Interface Engineering in Multiphase Systems toward Synthetic Cells and Organelles: From Soft Matter Fundamentals to Biomedical Applications

Cell-mediated targeting drugs delivery systems

Development of Cell Spheroids by Advanced Technologies

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