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| 3. |
- Ali Doosti, Baharan, 1991, et al.
(författare)
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Ca2+ Gradient Induces Membrane Bending and Formation of Nanotubes in Giant Lipid Vesicles
- 2016
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Ingår i: Biophysical Journal. - : Elsevier BV. - 0006-3495 .- 1542-0086. ; 110:3, s. 584A-584A
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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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| 6. |
- Alizadehheidari, Mohammadreza, 1987, et al.
(författare)
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Unfolding of nanoconfined circular DNA
- 2015
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Ingår i: BIOPHYSICAL JOURNAL. - : Elsevier BV. - 0006-3495 .- 1542-0086. ; 108:2 Supplement 1
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 7. |
- Almaqwashi, A. A., et al.
(författare)
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Dissecting the Dynamic Pathways of Stereoselective DNA Threading Intercalation
- 2016
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Ingår i: Biophysical Journal. - : Elsevier BV. - 0006-3495 .- 1542-0086. ; 110:6, s. 1255-1263
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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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| 13. |
- Badell, Maria Valldeperas, et al.
(författare)
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Lipid Sponge-Phase Nanoparticles as Carriers for Enzymes
- 2018
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Ingår i: Biophysical Journal. - : Cell Press. - 0006-3495 .- 1542-0086. ; 114:3, suppl 1, s. 15A-15A
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Immobilization of enzymes into different support materials has been widely studied as means to control their activity and stability. Here we will consider lipid liquid crystalline phases as enzyme carriers, as they have been demonstrated to have a high potential in a range of applications such as drug delivery, protein encapsulation or crystallization thanks to the wide range of self-assembly structures they can form, which have cavities of nano-scale dimensions. Furthermore, such structures have also been observed in a range of living organisms. Although, reverse cubic or hexagonal lipid aqueous phase can be used to entrap smaller biomolecules, it is still challenging to encapsulate bioactive macromolecules, such as proteins. Here, we will present a novel lipid system able to form highly swollen sponge phases (L3), with aqueous pores up to 13 nm of diameter. We will show that this structure is preserved even in excess aqueous solution, where they form sponge-like nanoparticles (L3 NPs) in which two enzymes of different sizes, Aspartic protease and beta-galactosidase (34 KDa and 460 KDa, respectively), could be included. To reveal the nature of the interaction between the enzymes and the lipid matrix, we studied the adsorption of both proteins on the lipid layers formed by the L3 NPs. The results will be discussed in terms of the ability of these nanoparticles to encapsulate and release of the proteins in the lipid matrix.
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| 15. |
- Bano, Fouzia, et al.
(författare)
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Single-molecule unbinding forces between the polysaccharide hyaluronan and its binding proteins
- 2018
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Ingår i: Biophysical Journal. - : Biophysical society. - 0006-3495 .- 1542-0086. ; 114:12, s. 2910-2922
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Tidskriftsartikel (refereegranskat)abstract
- The extracellular polysaccharide hyaluronan (HA) is ubiquitous in all vertebrate tissues, where its various functions are encoded in the supramolecular complexes and matrices that it forms with HA-binding proteins (hyaladherins). In tissues, these supramolecular architectures are frequently subjected to mechanical stress, yet how this affects the intermolecular bonding is largely unknown. Here, we used a recently developed single-molecule force spectroscopy platform to analyze and compare the mechanical strength of bonds between HA and a panel of hyaladherins from the Link module superfamily, namely the complex of the proteoglycan aggrecan and cartilage link protein, the proteoglycan versican, the inflammation-associated protein TSG-6, the HA receptor for endocytosis (stabilin-2/HARE), and the HA receptor CD44. We find that the resistance to tensile stress for these hyaladherins correlates with the size of the HA-binding domain. The lowest mean rupture forces are observed for members of the type A subgroup (i.e., with the shortest HA-binding domains; TSG-6 and HARE). In contrast, the mechanical stability of the bond formed by aggrecan in complex with cartilage link protein (two members of the type C subgroup, i.e., with the longest HA-binding domains) and HA is equal or even superior to the high affinity streptavidin⋅biotin bond. Implications for the molecular mechanism of unbinding of HA⋅hyaladherin bonds under force are discussed, which underpin the mechanical properties of HA⋅hyaladherin complexes and HA-rich extracellular matrices.
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| 17. |
- Bengtsson, Elina, et al.
(författare)
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Altered Structural State of Actin Filaments Upon MYOSIN II Binding
- 2015
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Ingår i: Biophysical Journal. - : Biophysical Society. - 0006-3495 .- 1542-0086. ; 108:2 Suppl. 1, s. 299A-300A
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The paths of actin filaments propelled over a heavy meromyosin (HMM) surface in the in vitro motility assay (IVMA) can statistically be described by a path persistence length (LPP) and has been hypothesized to be proportional to the flexural rigidity of the filaments. Here, we have studied the LPP at high (130 mM) ionic strength along with the persistence length of actin filaments in solution (LPS) to elucidate how HMM binding affects the flexural rigidity of actin filaments. Characterization and control of material properties, such as the path persistence length, is useful in engineered devices that takes advantages of the function of the muscle contractile proteins e.g. for biocomputation. It has been suggested that myosin binding reduces Lpp for phalloidin stabilizedact in filaments. This is consistent with the results presented here where the phalloidin stabilized actin filaments rigidity is reduced to the level of phalloidin free actin filaments in the IVMA. Further, reducing the MgATP concentration in the IVMA would increase the HMM head density along the actin filament hence making the effect of myosin binding more pronounced. A reduced [MgATP] from 1 mM to 0.02-0.05 mM did indeed reduce the LPP from 10-12 mm to 6-7 mm for both phalloidin-stabilized and phalloidin free actin filaments. Additionally, we found a negative correlation between the LPS and the [HMM]/actin ratio. However, this [HMM] dependent reduction observed in LPS was too small to account for the reduction in LPP seen with reduced [MgATP] in the IVMA. Monte-Carlo simulations and theoretical analysis revealed that the large reduction in LPP is consistent with the idea that every head attachment adds an extra angular displacement.(Support from EU-FP7-FET-ABACUS grant number 613044).
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| 18. |
- Bengtsson, Elina, et al.
(författare)
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Myosin-Induced Gliding Patterns at Varied [MgATP] Unveil a Dynamic Actin Filament
- 2016
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Ingår i: Biophysical Journal. - : Elsevier BV. - 0006-3495 .- 1542-0086. ; 111:7, s. 1465-1477
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Tidskriftsartikel (refereegranskat)abstract
- Actin filaments have key roles in cell motility but are generally claimed to be passive interaction partners in actin-myosin -based motion generation. Here, we present evidence against this static view based on an altered myosin-induced actin filament gliding pattern in an in vitro motility assay at varied [MgATP]. The statistics that characterize the degree of meandering of the actin filament paths suggest that for [MgATP] >= 0.25 mM, the flexural rigidity of heavy meromyosin (HMM)-propelled actin filaments is similar (without phalloidin) or slightly lower (with phalloidin) than that of HMM-free filaments observed in solution without surface tethering. When [MgATP] was reduced to <= 0.1 mM, the actin filament paths in the in vitro motility assay became appreciably more winding in both the presence and absence of phalloidin. This effect of lowered [MgATP] was qualitatively different from that seen when HMM was mixed with ATP-insensitive, N-ethylmaleimide-treated HMM (NEM-HMM; 25-30%). In particular, the addition of NEM-HMM increased a non-Gaussian tail in the path curvature distribution as well as the number of events in which different parts of an actin filament followed different paths. These effects were the opposite of those observed with reduced [MgATP]. Theoretical modeling suggests a 30-40% lowered flexural rigidity of the actin filaments at [MgATP] <= 0.1 mM and local bending of the filament front upon each myosin head attachment. Overall, the results fit with appreciable structural changes in the actin filament during actomyosin-based motion generation, and modulation of the actin filament mechanical properties by the dominating chemomechanical actomyosin state.
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| 20. |
- Blau, Christian, et al.
(författare)
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Gromaps: A Gromacs-Based Toolset to Analyse Density Maps Derived from Molecular Dynamics Simulations
- 2019
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Ingår i: Biophysical Journal. - : Elsevier BV. - 0006-3495 .- 1542-0086. ; 116:1, s. 4-11
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Tidskriftsartikel (refereegranskat)abstract
- We introduce a computational toolset, named GROmaρs, to obtain and compare time-averaged density maps from molecular dynamics simulations. GROmaρs efficiently computes density maps by fast multi-Gaussian spreading of atomic densities onto a three-dimensional grid. It complements existing map-based tools by enabling spatial inspection of atomic average localization during the simulations. Most importantly, it allows the comparison between computed and reference maps (e.g., experimental) through calculation of difference maps and local and time-resolved global correlation. These comparison operations proved useful to quantitatively contrast perturbed and control simulation data sets and to examine how much biomolecular systems resemble both synthetic and experimental density maps. This was especially advantageous for multimolecule systems in which standard comparisons like RMSDs are difficult to compute. In addition, GROmaρs incorporates absolute and relative spatial free-energy estimates to provide an energetic picture of atomistic localization. This is an open-source GROMACS-based toolset, thus allowing for static or dynamic selection of atoms or even coarse-grained beads for the density calculation. Furthermore, masking of regions was implemented to speed up calculations and to facilitate the comparison with experimental maps. Beyond map comparison, GROmaρs provides a straightforward method to detect solvent cavities and average charge distribution in biomolecular systems. We employed all these functionalities to inspect the localization of lipid and water molecules in aquaporin systems, the binding of cholesterol to the G protein coupled chemokine receptor type 4, and the identification of permeation pathways through the dermicidin antimicrobial channel. Based on these examples, we anticipate a high applicability of GROmaρs for the analysis of molecular dynamics simulations and their comparison with experimentally determined densities.
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