Current Opinion in Cell Biology最新文献

Eukaryotic nuclei are structured into sub-compartments orchestrating various cellular functions. The nucleolus is the largest nuclear organelle: a biomolecular condensate with an architecture composed of immiscible fluids facilitating ribosome biogenesis. The nucleolus forms upon the transcription of the repetitive ribosomal RNA genes (rDNA) that cluster in this compartment. rDNA is intrinsically unstable and prone to rearrangements and copy number variation. Upon DNA damage, a specialized nucleolar-DNA Damage Response (n-DDR) is activated: nucleolar transcription is inhibited, the architecture is rearranged, and rDNA is relocated to the nucleolar periphery. Recent data have highlighted how the composition of nucleoli, its structure, chemical and physical properties, contribute to rDNA stability. In this mini-review we focus on recent data that start to reveal how nucleolar composition and the n-DDR work together to ensure rDNA integrity.

Intermediate filaments (IFs) are integral to the cell cytoskeleton, supporting cellular mechanical stability. Unlike other cytoskeletal components, the detailed structure of assembled IFs has yet to be resolved. This review highlights new insights, linking the complex IF hierarchical assembly to their mechanical properties and impact on cellular functions. While we focus on vimentin IFs, we draw comparisons to keratins, showcasing the distinctive structural and mechanical features that underlie their unique mechanical responses.

Mathematical models are indispensable for disentangling the interactions through which biological components work together to generate the forces and flows that position, mix, and distribute proteins, nutrients, and organelles within the cell. To illuminate the ever more specific questions studied at the edge of biological inquiry, such models inevitably become more complex. Solving, simulating, and learning from these more realistic models requires the development of new analytic techniques, numerical methods, and scalable software. In this review, we discuss some recent developments in tools for understanding how large numbers of cytoskeletal filaments, driven by molecular motors and interacting with the cytoplasm and other structures in their environment, generate fluid flows, instabilities, and material deformations which help drive crucial cellular processes.

In silico labeling is the computational cross-modality image translation where the output modality is a subcellular marker that is not specifically encoded in the input image, for example, in silico localization of organelles from transmitted light images. In principle, in silico labeling has the potential to facilitate rapid live imaging of multiple organelles with reduced photobleaching and phototoxicity, a technology enabling a major leap toward understanding the cell as an integrated complex system. However, five years have passed since feasibility was attained, without any demonstration of using in silico labeling to uncover new biological insight. In here, we discuss the current state of in silico labeling, the limitations preventing it from becoming a practical tool, and how we can overcome these limitations to reach its full potential.

Intracellular organization is a highly regulated homeostatic state maintained to ensure eukaryotic cells’ correct and efficient functioning. Thanks to decades of research, vast knowledge of the proteins involved in intracellular transport and organization has been acquired. However, how these influence and potentially regulate the intracellular mechanical properties of the cell is largely unknown. There is a deep knowledge gap between the understanding of cortical mechanics, which is accessible by a series of experimental tools, and the intracellular situation that has been largely neglected due to the difficulty of performing intracellular mechanics measurements. Recently, tools required for such quantitative and localized analysis of intracellular mechanics have been introduced. Here, we review how these approaches and the resulting viscoelastic models lead the way to a full mechanical description of the cytoplasm, which is instrumental for a quantitative characterization of the intracellular life of cells.

Nonvesicular lipid transport among different membranes or membrane domains plays crucial roles in lipid homeostasis and organelle biogenesis. However, the forces that drive such lipid transport are not well understood. We propose that lipids tend to flow towards the membrane area with a higher membrane protein density in a process termed lipid osmosis. This process lowers the membrane tension in the area, resulting in a membrane tension difference called osmotic membrane tension. We examine the thermodynamic basis and experimental evidence of lipid osmosis and osmotic membrane tension. We predict that lipid osmosis can drive bulk lipid flows between different membrane regions through lipid transfer proteins, scramblases, or similar barriers that selectively pass lipids but not membrane proteins. We also speculate on the biological functions of lipid osmosis. Finally, we explore other driving forces for lipid transfer and describe potential methods and systems to further test our theory.

Living organisms can detect and respond to physical forces at the cellular level. The pathways that transmit these forces to the nucleus allow cells to react quickly and consistently to environmental changes. Mechanobiology involves the interaction between physical forces and biological processes and is crucial for driving embryonic development and adapting to environmental cues during adulthood. Molecular studies have shown that cells can sense mechanical signals directly through membrane receptors linked to the cytoskeleton or indirectly through biochemical cascades that can influence gene expression for environmental adaptation. This review will explore the role of epigenetic modifications, emphasizing the 3D genome architecture and nuclear structures as responders to mechanical stimuli, which ensure cellular memory and adaptability. Understanding how mechanical cues are transduced and regulate cell functioning, governing processes such as cell programming and reprogramming, is essential for advancing our knowledge of human diseases.

Phosphoinositides broadly impact membrane dynamics, signal transduction and cellular physiology. The orchestration of signaling complexity by this seemingly simple metabolic pathway remains an open question. It is increasingly evident that comprehending the complexity of the phosphoinositides metabolic network requires a systems view based on nonlinear dynamics, where the products of metabolism can either positively or negatively modulate enzymatic function. These feedback and feedforward loops may be paradoxical, leading to counterintuitive effects. In this review, we introduce the framework of nonlinear dynamics, emphasizing distinct dynamical regimes such as the excitable state, oscillations, and mixed-mode oscillations—all of which have been experimentally observed in phosphoinositide metabolisms. We delve into how these dynamical behaviors arise from one or multiple network motifs, including positive and negative feedback loops, coherent and incoherent feedforward loops. We explore the current understanding of the molecular circuits responsible for these behaviors. While mapping these circuits presents both conceptual and experimental challenges, redefining cellular behavior based on dynamical state, lipid fluxes, time delay, and network topology is likely essential for a comprehensive understanding of this fundamental metabolic network.

Caveolae are atypical plasma membrane invaginations that take part in lipid sorting and regulation of oxidative and mechanical plasma membrane stress. Caveola formation requires caveolin, cavin, and specific lipid types. The recent advances in understanding the structure and assembly of caveolin and cavin complexes within the membrane context have clarified the fundamental processes underlying caveola biogenesis. In addition, the curvature of the caveola membrane is controlled by the regulatory proteins EHD2, pacsin2, and dynamin2, which also function to restrain the scission of caveolae from the plasma membrane (PM). Here, this is integrated with novel insights on caveolae as lipid and mechanosensing complexes that can dynamically flatten or disassemble to counteract mechanical, and oxidative stress.