A Tunable Palette of Molecular Rotors Allows Multicolor, Ratiometric Fluorescence Imaging and Direct Mapping of Mitochondrial Heterogeneity.

Environment-sensitive molecular probes offer the potential for a comprehensive mapping of the complex cellular milieu. We present here a radically new strategy of multiplexing highly sensitive, spectrally tuned fluorescent dyes for sensing cellular microenvironment. To achieve this multicolor, ratiometric cellular imaging, we first developed a series of highly sensitive, tunable molecular rotors for mitochondrial imaging, with emission wavelengths spanning the visible spectrum.

The Gelsolin Pathogenic D187N Mutant Exhibits Altered Conformational Stability and Forms Amyloidogenic Oligomers.

Gelsolin is an actin-severing protein that attains an open functional conformation in the presence of Ca or low pH. Mutations (D187N/Y) in the second domain of gelsolin trigger the proteolytic pathway producing amyloidogenic fragments that form the pathological hallmark of gelsolin amyloidosis and lattice corneal dystrophy type 2 (LCD2). Here, we show that the D187N mutant gelsolin in a Ca depleted, low pH-activated, open conformation could assemble into amyloidogenic oligomers without necessarily undergoing the specific proteolytic step.