Caveolin-1 controls mitochondrial damage and ROS production by regulating fission - fusion dynamics and mitophagy.

As essential regulators of mitochondrial quality control, mitochondrial dynamics and mitophagy play key roles in maintenance of metabolic health and cellular homeostasis. Here we show that knockdown of the membrane-inserted scaffolding and structural protein caveolin-1 (Cav-1) and expression of tyrosine 14 phospho-defective Cav-1 mutant (Y14F), as opposed to phospho-mimicking Y14D, altered mitochondrial morphology, and increased mitochondrial matrix mixing, mitochondrial fusion and fission dynamics as well as mitophagy in MDA-MB-231 triple negative breast cancer cells. Further, we found that interaction of Cav-1 with mitochondrial fusion/fission machinery Mitofusin 2 (Mfn2) and Dynamin related protein 1 (Drp1) was enhanced by Y14D mutant indicating Cav-1 Y14 phosphorylation prevented Mfn2 and Drp1 translocation to mitochondria. Moreover, limiting mitochondrial recruitment of Mfn2 diminished formation of the PINK1/Mfn2/Parkin complex required for initiation of mitophagy resulting in accumulation of damaged mitochondria and ROS (mtROS). Thus, these studies indicate that phospho-Cav-1 may be an important switch mechanism in cancer cell survival which could lead to novel strategies for complementing cancer therapies.

Fabrication of Poly(ethylene glycol) Hydrogel Structures for Pharmaceutical Applications using Electron beam and Optical Lithography.

Soft-polymer based microparticles are currently being applied in many biomedical applications, ranging from bioimaging and bioassays to drug delivery carriers. As one class of soft-polymers, hydrogels are materials, which can be used for delivering drug cargoes and can be fabricated in controlled sizes. Among the various hydrogel-forming polymers, poly(ethylene glycol) (PEG) based hydrogel systems are widely used due to their negligible toxicity and limited immunogenic recognition. Physical and chemical properties of particles (i.e., particle size, shape, surface charge, and hydrophobicity) are known to play an important role in cell-particle recognition and response. To understand the role of physicochemical properties of PEG-based hydrogel structures on cells, it is important to have geometrically precise and uniform hydrogel structures. To fabricate geometrically uniform structures, we have employed electron beam lithography (EBL) and ultra-violet optical lithography (UVL) using PEG or PEG diacrylate polymers. These hydrogel structures have been characterized by scanning electron microscopy (SEM), atomic force microscopy (AFM), optical microscopy, and attenuated total reflection Fourier-transform infrared spectroscopy (ATR-FTIR) confirming control of chemistry, size, and shape.