Fibril-type aggregates of tau occur in Alzheimer's disease (AD) and dozens of tauopathies. Fibrils catalyze aggregation by prion-like seeding, which in part underlies disease progression. Seeding by recombinant and brain-derived tau fibrils is measured using biosensor cells that express aggregation-prone tau mutants fused with fluorescent reporter proteins. Seeding results in a punctated phenotype that is well established, but evidence that fluorescent tau fusion proteins from biosensor cells assemble into fibril-type structures is lacking. We investigated the effects of seeding on fibril formation by biosensor cells. Fluorescent punctated cell phenotypes that were catalyzed persisted with varying stabilities. Seeded cells bearing punctated phenotypes yielded sarkosyl-insoluble fibrils, although non-seeded cells did not. ImmunoEM of cell-purified fibrils shows that GFP localizes to the proteolytically sensitive fuzzy coat of tau fibrils. The presented data offer compelling evidence that fluorescent puncta are fibril-type aggregates of tau that result from prion-like seeding.
Sensitive detection of incident acoustic waves over a broad frequency band offers a faithful representation of photoacoustic pressure transients of biological microstructures. Here, we propose a plasmon waveguide resonance sensor for responding to the photoacoustic impulses. By sequentially depositing Au, MgF, and SiO films on a coverslip, a composite waveguide layer produces a tightly confined optical evanescent field at the SiO-water interface with extremely strong electric field intensity, enabling the retrieval of photoacoustic signals with an estimated noise-equivalent-pressure (NEP) sensitivity of ∼92 Pa and a -6-dB bandwidth of ∼208 MHz.
The application of upconversion nanoparticles (UCNPs) for cell and tissue analysis requires a comprehensive understanding of their interactions with biological entities to prevent toxicity or harmful effects. Whereas most studies focus on cancer cells, this work addresses non-cancerous cells with their regular in vitro physiology. Since it is generally accepted that surface chemistry largely determines biocompatibility in general and uptake of nanomaterials in particular, two bilayer surface coatings with different surface shielding properties have been studied: (i) a phospholipid bilayer membrane (PLM) and (ii) an amphiphilic polymer (AP).
Heat shock protein A1A (HSPA1A) is a molecular chaperone crucial in cell survival. In addition to its cytosolic functions, HSPA1A translocates to heat-shocked and cancer cells' plasma membrane (PM). In cancer, PM-localized HSPA1A (mHSPA1A) is associated with increased tumor aggressiveness and therapeutic resistance, suggesting that preventing its membrane localization could have therapeutic value.
Nuclear deformation by osmotic shock or necrosis activates the cytosolic phospholipase A2 (cPla2) nuclear shape sensing pathway, a key regulator of tissue inflammation and repair. Ca²⁺ and inner nuclear membrane (INM) tension (T ) are believed to mediate nucleoplasmic cPla2 activation. The concept implies that T persists long enough to stimulate cPla2-INM adsorption.
Peroxynitrite (ONOO) and viscosity are critical indicators of lysosome functionality, intimately linked to numerous diseases' pathophysiological processes. Hence, creating reliable analytical techniques to observe fluctuations in lysosomal ONOO and viscosity is highly important. This study presents the development of a novel naphthalimide-based fluorescent probe, Nap-Cy, specifically designed to target lysosomes and simultaneously detect both ONOO and viscosity.
