Towards cellular-scale structural modeling, multiscale biomolecular simulation is gaining much attention. Here, I review methodological aspects of coarse-grained (CG) biomolecular simulations. I begin with conceptual argument of coarse graining for proteins where the idea behind Gō models is discussed. Then, statistical physics and theories of coarse graining are described. I then exemplify a class of CG models for proteins, nucleic acids, and lipids, where about 10 non-hydrogen atoms are grouped into one CG particles. Finally, I discuss three sources of speeding up by coarse graining.

Microscopic heterogeneity of the extracellular mechanical environment is an essential factor in controlling cell migration such as in morphogenesis, wound healing, and cancer metastasis. For example, a monotonic, microscopic stiffness gradient can induce directional cell migration, so-called durotaxis. However, it has been unclear how cell migration is modulated under a cell-scale heterogeneity of matrix-elasticity. Here, to understand the cell migration on a matrix with heterogeneous elasticity distribution, we review experiments about the dynamics of cell shape and motion on hydrogels with various elasticity distributions, and theoretical works for the cell migration based on a model of cell-shaping dynamics.

Mitochondria play a role as intracellular calcium stores as well as energy conversion functions. Mitochondrial calcium uptake is mediated by mitochondrial calcium ion channel, “calcium uniporter”. In this decade, the molecular composition of the calcium uniporter complex was discovered; the calcium uniporter consists of the 7 subunits. Using the yeast reconstitution technique, we showed that MCU and EMRE are core subunits of the complex. The yeast reconstitution technique has also enabled us to perform detailed structure-function analysis of the MCU and EMRE. In this review, we will discuss the molecular mechanism of mitochondrial Ca²⁺ uptake.

Pulsed electric fields (PEFs) have been widely utilized in life sciences, particularly for electroporation. Recent advances in electrical engineering enable the use of ultrashort PEFs in duration of nanoseconds (referred to as nanosecond PEFs, nsPEFs). Unlike milli- to microsecond PEFs used for electroporation, nsPEFs does not generate membrane pores suited for macromolecule transfer. Instead, nsPEFs can elicit various cellular responses in an intensity-dependent manner. nsPEFs are increasingly recognized as a novel physical means with unique biological actions. This review provides an overview of cellular responses to nsPEFs and possible biomedical applications of nsPEFs.

In a previous report, the author developed a synthetic biology molecular tool, iPOLYMER, which produces hydrogel condensates consisting of two polypeptide chains in living cells, in a stimulus-dependent manner. Functionalizing the iPOLYMER polypeptides with an RNA-binding domain successfully reconstituted a typical example of biomolecular condensates, stress granules, in living cells under a stress-free condition. In the current review, achievements made possible by iPOLYMER are summarized, with reference to a brief history of biomolecular condensate research. Future prospects, as well as technical challenges, of synthetic biological approaches to the novel class of intracellular structures are also described.