William Moerner, Doctoral Dissertation Advisor (AC)
Opposing Effects of Cohesin and Transcription on CTCF Organization Revealed by Super-resolution Imaging.
CCCTC-binding factor (CTCF) and cohesin play critical roles in organizing mammalian genomes into topologically associating domains (TADs). Here, by combining genetic engineering with quantitative super-resolution stimulated emission depletion (STED) microscopy, we demonstrate that in living cells, CTCF forms clusters typically containing 2-8 molecules. A fraction of CTCF clusters, enriched for those with ≥3 molecules, are coupled with cohesin complexes with a characteristic physical distance suggestive of a defined molecular interaction. Acute degradation of the cohesin unloader WAPL or transcriptional inhibition (TI) result in increased CTCF clustering. Furthermore, the effect of TI on CTCF clusters is alleviated by the acute loss of the cohesin subunit SMC3. Our study provides quantitative characterization of CTCF clusters in living cells, uncovers the opposing effects of cohesin and transcription on CTCF clustering, and highlights the power of quantitative super-resolution microscopy as a tool to bridge the gap between biochemical and genomic methodologies in chromatin research.
View details for DOI 10.1016/j.molcel.2020.10.001
View details for PubMedID 33091336
T-Plastin reinforces membrane protrusions to bridge matrix gaps during cell migration.
2020; 11 (1): 4818
Migrating cells move across diverse assemblies of extracellular matrix (ECM) that can be separated by micron-scale gaps. For membranes to protrude and reattach across a gap, actin filaments, which are relatively weak as single filaments, must polymerize outward from adhesion sites to push membranes towards distant sites of new adhesion. Here, using micropatterned ECMs, we identify T-Plastin, one of the most ancient actin bundling proteins, as an actin stabilizer that promotes membrane protrusions and enables bridging of ECM gaps. We show that T-Plastin widens and lengthens protrusions and is specifically enriched in active protrusions where F-actin is devoid of non-muscle myosin II activity. Together, our study uncovers critical roles of the actin bundler T-Plastin to promote protrusions and migration when adhesion is spatially-gapped.
View details for DOI 10.1038/s41467-020-18586-3
View details for PubMedID 32968060
Resolving and Controlling Photoinduced Ultrafast Solvation in the Solid State
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
2017; 8 (17): 4183–90
Solid-state solvation (SSS) is a solid-state analogue of solvent-solute interactions in the liquid state. Although it could enable exceptionally fine control over the energetic properties of solid-state devices, its molecular mechanisms have remained largely unexplored. We use ultrafast transient absorption and optical Kerr effect spectroscopies to independently track and correlate both the excited-state dynamics of an organic emitter and the polarization anisotropy relaxation of a small polar dopant embedded in an amorphous polystyrene matrix. The results demonstrate that the dopants are able to rotationally reorient on ultrafast time scales following light-induced changes in the electronic configuration of the emitter, minimizing the system energy. The solid-state dopant-emitter dynamics are intrinsically analogous to liquid-state solvent-solute interactions. In addition, tuning the dopant/polymer pore ratio offers control over solvation dynamics by exploiting molecular-scale confinement of the dopants by the polymer matrix. Our findings will enable refined strategies for tuning optoelectronic material properties using SSS and offer new strategies to investigate mobility and disorder in heterogeneous solid and glassy materials.
View details for DOI 10.1021/acs.jpclett.7b01689
View details for Web of Science ID 000410600600035
View details for PubMedID 28829138
- Tuning Thermally Activated Delayed Fluorescence Emitter Photophysics through Solvation in the Solid State ACS ENERGY LETTERS 2017; 2 (7): 1526–33
Phase Behavior of Magnetic Nanocolloids of Different Sizes Suspended in an Apolar Solvent.
Langmuir : the ACS journal of surfaces and colloids
2017; 33 (42): 11366–76
We employ classical density functional theory (DFT) to investigate the phase behavior and composition of binary mixtures; each compound consists of hard spheres of different sizes with superimposed dispersion attraction. In addition to the dispersion attraction, molecules of one component carry an additional three-dimensional magnetic "spin" where the orientation-dependent spin-spin interaction is accounted for by the Heisenberg model. We are treating the excess free energy using a modified mean-field approximation (second virial coefficient) for the orientation-dependent pair correlation function. Depending on the concentration of the magnetic particles, the strength of the spin-spin coupling, and the size ratio of the particles, the model predicts the formation of ordered (polar) phases in addition to the more conventional gas and isotropic liquid phases. Key features of our model are a particle-size dependent shift of the gas-liquid critical point (critical temperature and density) and a change in the width of the phase diagram. In the near-critical region, the latter can be analyzed quantitativly in terms of an effective critical exponent βeff that may differ from the classical critical exponent [Formula: see text]; the classical value is attained in the immediate vicinity of the critical point as it must. The deviation between βeff and β can be linked to nontrivial composition effects along the phase boundaries.
View details for PubMedID 28764322