Brckner H. controlling cell behavior. By discussing the correlation between molecular assemblies in nature and the assemblies of small molecules in cell milieu, illustrating the functions of MMP19 the assemblies of small molecules, and summarizing some guiding principles, we GLUFOSFAMIDE hope this review will stimulate more molecular scientists to explore the bioinspired self-assembly of small molecules in cell milieu. Graphical abstract This review provides new insights and approaches for exploring bioinspired self-assembly of small molecules in cellular milieu. Introduction Nature, an inexhaustible source, inspires us to explore the world we live in. Chemists, materials scientists, as well as biologists are all interested in dispelling the mysterious veil of nature (e.g., living organisms, especially GLUFOSFAMIDE cells) at molecular levels because nature has evolved elaborate machineries1 that largely consist of supramolecular assemblies of biomacromolecules and carry out sophisticated biological tasks in all organisms. The advances in molecular cell biology have contributed to the development of a new subject (or strategy)bioinspiration, which involves multiple disciplines to nucleate new ideas for research.2 To mimic the properties of biological systems by non-living systems, many disciplines use the concept of self-assembly, which is a prevalent process in cells and a common phenomenon of nature. In the context of molecules and cells, self-assembly is the autonomous organization of individual components into patterns and functional nanostructures through non-covalent interactions with the balance of both thermodynamic and global (or local) equilibrium. With GLUFOSFAMIDE the increasing understanding of biological systems (especially biomacromolecules assemblies1) and the development of new technologies (e.g., cryo-EM), more and more innovative materials are bio-inspired molecular assemblies. Over the last two decades, inspired by biological organisms, from cells to sub-cell organelles, chemists and material scientists have extensively explored artificial functional macromolecules (especially functional artificial proteins and polymers3) for bottom-up GLUFOSFAMIDE self-assembly to form specific nanostructures. The understanding of the assemblies of biomacromolecules (e.g., DNA, RNA, and proteins) at a molecular level and the intrinsic forces for the self-assembly of small molecules of cells (e.g., lipids or cholesterols) have provided useful insights on how these simple components self-assemble to form highly ordered and precisely (both spatially and temporally) controlled structures (Fig. 1) in an organism,1 which has stimulated the exploration of assemblies of small molecules to mimic the properties and structures of living systems for applications in different fields to benefit humans, such as liposomes for drug delivery. Many efforts have focused on understanding and controlling self-assemblies of small molecules with non-biological stimuli in vitro (i.e., cell free setting) over the last several decades, and the progress of these studies has resulted in a large library of candidates that promise biomedical applications for the assemblies of small molecules, as documented in several reviews.4 Moreover, recent findings in biology have provided exciting insights for using the assemblies of small molecules to modulate essential cellular processes. For example, lipid rafts modulating apoptosis (i.e., the process of programmed cell death)5 or antibiotics inhibiting bacteria6 are endogenous or naturally occurring processes. They have inspired the development of self-assembly of man-made small molecules in cell milieu to act as multifaceted entities that interact with multiple proteins and control the fates of cells. In fact, such developments have progressed considerably to warrant a review to illustrate the concepts and the design principles for exploring self-assemblies of man-made small molecules in cell milieu. Open in a separate window Fig. 1 Schematic of endogenous molecular assemblies and their building blocks for inspiring self-assembly of small molecules in.