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Sökning: L773:0006 3495 > (2015-2019)

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  • Ali Doosti, Baharan, 1991, et al. (författare)
  • Ca2+ Gradient Induces Membrane Bending and Formation of Nanotubes in Giant Lipid Vesicles
  • 2016
  • Ingår i: Biophysical Journal. - : Elsevier BV. - 0006-3495 .- 1542-0086. ; 110:3, s. 584A-584A
  • Tidskriftsartikel (refereegranskat)abstract
    • Reshaping and bending of the cell membrane is imperative in many processes such as cell division, filopodia formation, and endocytosis. Understanding these shape transitions, will help to elucidate the underlying mechanisms of these essential cellular processes. In our work, we investigate an interplay between cell membrane morphology and chemical stimulation by constructing a biomimetic model system. More specifically, giant lipid vesicles were exposed to a chemical gradient of Ca2+, which was established over the membrane surface.
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  • Alizadehheidari, Mohammadreza, 1987, et al. (författare)
  • Unfolding of nanoconfined circular DNA
  • 2015
  • Ingår i: BIOPHYSICAL JOURNAL. - : Elsevier BV. - 0006-3495 .- 1542-0086. ; 108:2 Supplement 1
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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  • Almaqwashi, A. A., et al. (författare)
  • Dissecting the Dynamic Pathways of Stereoselective DNA Threading Intercalation
  • 2016
  • Ingår i: Biophysical Journal. - : Elsevier BV. - 0006-3495 .- 1542-0086. ; 110:6, s. 1255-1263
  • Tidskriftsartikel (refereegranskat)abstract
    • DNA intercalators that have high affinity and slow kinetics are developed for potential DNA-targeted therapeutics. Although many natural intercalators contain multiple chiral subunits, only intercalators with a single chiral unit have been quantitatively probed. Dumbbell-shaped DNA threading intercalators represent the next order of structural complexity relative to simple intercalators, and can provide significant insights into the stereoselectivity of DNA-ligand intercalation. We investigated DNA threading intercalation by binuclear ruthenium complex [mu-dppzip(phen)(4)Ru-2](4+) (Piz). Four Piz stereoisomers are defined by the chirality of the intercalating subunit (Ru(phen)(2)dppz) and the distal subunit (Ru(phen)(2)ip), respectively, each of which can be either right-handed (Delta) or left-handed (Lambda). We used optical tweezers to measure single DNA molecule elongation due to threading intercalation, revealing force-dependent DNA intercalation rates and equilibrium dissociation constants. The force spectroscopy analysis provided the zero-force DNA binding affinity, the equilibrium DNA-ligand elongation Delta x(eq), and the dynamic DNA structural deformations during ligand association x(on) and dissociation x(off). We found that Piz stereoisomers exhibit over 20-fold differences in DNA binding affinity, from a K-d of 27 +/- 3 nM for (Delta,Lambda)-Piz to a K-d of 622 +/- 55 nM for (Lambda,Delta)-Piz. The striking affinity decrease is correlated with increasing Delta x(eq) from 0.30 +/- 0.02 to 0.48 +/- 0.02 nm and x(on) from 0.25 +/- 0.01 to 0.46 +/- 0.02 nm, but limited x(off) changes. Notably, the affinity and threading kinetics is 10-fold enhanced for right-handed intercalating subunits, and 2- to 5-fold enhanced for left-handed distal subunits. These findings demonstrate sterically dispersed transition pathways and robust DNA structural recognition of chiral intercalators, which are critical for optimizing DNA binding affinity and kinetics.
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