Mammalian cells frequently migrate through tight spaces during normal embryogenesis, wound healing, diapedesis, or in pathological situations such as metastasis. Nuclear size and shape are important factors in regulating the mechanical properties of cells during their migration through such tight spaces. At the onset of migratory behavior, cells often initiate the expression of vimentin, an intermediate filament protein that polymerizes into networks extending from a juxtanuclear cage to the cell periphery. However, the role of vimentin intermediate filaments (VIFs) in regulating nuclear shape and mechanics remains unknown. Here, we use wild-type and vimentin-null mouse embryonic fibroblasts to show that VIFs regulate nuclear shape and perinuclear stiffness, cell motility in 3D, and the ability of cells to resist large deformations. These changes increase nuclear rupture and activation of DNA damage repair mechanisms, which are rescued by exogenous reexpression of vimentin. Our findings show that VIFs provide mechanical support to protect the nucleus and genome during migration.

Phosphoinositides play a crucial role in regulating many cellular functions, such as actin dynamics, signaling, intracellular trafficking, membrane dynamics, and cell–matrix adhesion. Central to this process is phosphatidylinositol bisphosphate (PIP2). The levels of PIP2 in the membrane are rapidly altered by the activity of phosphoinositide-directed kinases and phosphatases, and it binds to dozens of different intracellular proteins. Despite the vast literature dedicated to understanding the regulation of PIP2 in cells over past 30 years, much remains to be learned about its cellular functions. In this review, we focus on past and recent exciting results on different molecular mechanisms that regulate cellular functions by binding of specific proteins to PIP2 or by stabilizing phosphoinositide pools in different cellular compartments. Moreover, this review summarizes recent findings that implicate dysregulation of PIP2 in many diseases

Viscosity plays a critical role in cell morphology, dynamics and cell-substrate interaction.

Smart biomaterials have significantly impacted human healthcare by advancing the development of medical devices designed to function within human tissue, mimicking the behavior of natural tissues. While the intelligence of biomaterials has evolved from inert to active over the past few decades, smart biomaterials take this a step further by making their surfaces or bulk respond based on interactions with surrounding tissues, imparting outcomes similar to natural tissue functions. This interaction with the surrounding tissue helps in creating stimuli-responsive biomaterials, which can be useful in tissue engineering, regenerative medicine, autonomous drug delivery, orthopedics, and much more. Traditionally, material engineering focused on refining the static properties of biomaterials to accommodate them within the body without evoking an immune response, which was a major obstacle to their unrestricted operation. This review highlights and explains various engineering approaches currently under research for developing stimuli-responsive biomaterials that tune their outcomes based on responses to bodily factors like temperature, pH, and ion concentration or external factors like magnetism, light, and conductivity. Applications in soft and hard tissue engineering, 4D printing, and scaffold design are also discussed. The advanced application of microfluidics, like organ-on-a-chip models, extensively benefits from the intrinsic smart properties of biomaterials, which are also discussed below. The review further elaborates on how smart biomaterial engineering could revolutionize biosensor applications, thereby improving patient care quality. We delineate the limitations and key challenges associated with biomaterials, providing insights into the path forward and outlining future directions for developing next-generation biomaterials that will facilitate clinical translation.