S100A11 promotes focal adhesion disassembly via myosin II-driven contractility and Piezo1-mediated Ca2+ entry.

S100A11 is a small Ca2+-activatable protein known to localize along stress fibers (SFs). Analyzing S100A11 localization in HeLa and U2OS cells further revealed S100A11 enrichment at focal adhesions (FAs). Strikingly, S100A11 levels at FAs increased sharply, yet transiently, just before FA disassembly. Elevating intracellular Ca2+ levels with ionomycin stimulated both S100A11 recruitment and subsequent FA disassembly. However, pre-incubation with the non-muscle myosin II (NMII) inhibitor blebbistatin or with an inhibitor of the stretch-activatable Ca2+ channel Piezo1 suppressed S100A11 recruitment, implicating S100A11 in an actomyosin-driven FA recruitment mechanism involving Piezo1-dependent Ca2+ influx. Applying external forces on peripheral FAs likewise recruited S100A11 to FAs even if NMII activity was inhibited, corroborating the mechanosensitive recruitment mechanism of S100A11. However, extracellular Ca2+ and Piezo1 function were indispensable, indicating that NMII contraction forces act upstream of Piezo1-mediated Ca2+ influx, in turn leading to S100A11 activation and FA recruitment. S100A11-knockout cells display enlarged FAs and had delayed FA disassembly during cell membrane retraction, consistent with impaired FA turnover in these cells. Our results thus demonstrate a novel function for S100A11 in promoting actomyosin contractility-driven FA disassembly.

Remote Magnetic Control of Autophagy in Mouse B-Lymphoma Cells with Iron Oxide Nanoparticles.

Autophagy is the spontaneous degradation of intracellular proteins and organelles in response to nutrient deprivation. The phagocytosis of iron oxide nanoparticles (IONPs) results in intracellular degradation that can be exploited for use in cancer treatment. Non-invasive magnetic control has emerged as an important technology, with breakthroughs achieved in areas such as magneto-thermal therapy and drug delivery. This study aimed to regulate autophagy in mouse B-lymphoma cells (A20) through the incorporation of IONPs-quantum dots (QDs). We hypothesized that with the application of an external magnetic field after phagocytosis of IONPs-QDs, autophagy of intracellular IONPs-QDs could be regulated in a non-invasive manner and subsequently modulate the regulation of inflammatory responses. The potential of this approach as a cancer treatment method was explored. The application of IONPs and an external magnetic force enabled the non-invasive regulation of cell autophagy and modulation of the self-regulatory function of cells. The combination of non-invasive magnetic fields and nanotechnology could provide a new approach to cancer treatment.

Noninvasive Glucose Monitoring with a Contact Lens and Smartphone.

Diabetes has become a chronic metabolic disorder, and the growing diabetes population makes medical care more important. We investigated using a portable and noninvasive contact lens as an ideal sensor for diabetes patients whose tear fluid contains glucose. The key feature is the reversible covalent interaction between boronic acid and glucose, which can provide a noninvasive glucose sensor for diabetes patients. We present a phenylboronic acid (PBA)-based HEMA contact lens that exhibits a reversible swelling/shrinking effect to change its thickness. The difference in thickness can be detected in a picture taken with a smartphone and analyzed using software. Our novel technique offers the following capabilities: (i) non-enzymatic and continuous glucose detection with the contact lens; (ii) no need for an embedded circuit and power source for the glucose sensor; and (iii) the use of a smartphone to detect the change in thickness of the contact lens with no need for additional photo-sensors. This technique is promising for a noninvasive measurement of the glucose level and simple implementation of glucose sensing with a smartphone.

Enhanced Osteogenic Differentiation of Stem Cells on Phase-Engineered Graphene Oxide.

Graphene oxide (GO) has attracted significant interest as a template material for multiple applications due to its two-dimensional nature and established functionalization chemistries. However, for applications toward stem cell culture and differentiation, GO is often reduced to form reduced graphene oxide, resulting in a loss of oxygen content. Here, we induce a phase transformation in GO and demonstrate its benefits for enhanced stem cell culture and differentiation while conserving the oxygen content. The transformation results in the clustering of oxygen atoms on the GO surface, which greatly improves its ability toward substance adherence and results in enhanced differentiation of human mesenchymal stem cells toward the osteogenic lineage. Moreover, the conjugating ability of modified GO strengthened, which was examined by auxiliary osteogenic growth peptide conjugation. Overall, our work demonstrates GO's potential for stem cell applications while maintaining its oxygen content, which could enable further functionalization and fabrication of novel nano-biointerfaces.

Simultaneous drug delivery and cellular imaging using graphene oxide.

Graphene oxide (GO), a derivative of graphene, and its related nanomaterials have attracted much attention in recent years due to the excellent biocompatibility and large surface area of GO with abundant oxygen functional groups, which further enable it to serve as a nano-bio interface. Herein, we demonstrate the induction of blue fluorescence in GO suspensions via a mild thermal annealing procedure. Additionally, this procedure preserves the oxygen functional groups on the graphene plane which enables the conjugation of cancer drugs without obvious cytotoxicity. Consequently, we demonstrate the capability of GO to simultaneously play the dual-role of a: (i) cellular imaging agent and (ii) drug delivery agent in CT26 cancer cells without the need for additional fluorescent protein labeling. Our method offers a simple, controllable strategy to tune and enhance the fluorescence property of GO, which shows potential for biomedical applications and fundamental studies.