| 1. |
- A. Strumpfer, Johan, et al.
(author)
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Stretching of Twitchin Kinase
- 2012
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In: Biophysical Journal. - St. Louis, MO, United States : Cell Press. - 0006-3495 .- 1542-0086. ; 102:3 Supplement 1, s. 361a-362a
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Journal article (peer-reviewed)abstract
- The giant proteins from the titin family, that form cytoskeletal filaments, have emerged as key mechanotransducers in the sarcomere. These proteins contain a conserved kinase region, which is auto-inhibited by a C-terminal tail domain. The inhibitory tail domain occludes the active sites of the kinases, thus preventing ATP from binding. It was proposed that through application of a force, such as that arising during muscle contraction, the inhibitory tail becomes detached, lifting inhibition. The force-sensing ability of titin kinase was demonstrated in AFM experiments and simulations [Puchner, et al., 2008, PNAS:105, 13385], which showed indeed that mechanical forces can remove the autoinhibitory tail of titin kinase. We report here steered molecular dynamics simulations (SMD) of the very recently resolved crystal structure of twitchin kinase, containing the kinase region and flanking fibronectin and immuniglobulin domains, that show a variant mechanism. Despite the significant structural and sequence similarity to titin kinase, the autoinhibitory tail of twitchin kinase remains in place upon stretching, while the N-terminal lobe of the kinase unfolds. The SMD simulations also show that the detachment and stretching of the linker between fibronectin and kinase regions, and the partial extension of the autoinhibitory tail, are the primary force-response. We postulate that this stretched state, where all structural elements are still intact, may represent the physiologically active state.
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| 2. |
- Adler, Jeremy, et al.
(author)
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Quantification of Colocalisation; Co-Occurrence, Correlation, Empty Voxels, Regions of Interest and Thresholding
- 2014
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In: Biophysical Journal. - : Elsevier BV. - 0006-3495 .- 1542-0086. ; 106:2, s. 602A-602A
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Journal article (other academic/artistic)abstract
- Measuring colocalisation is not straightforward with a plethora of coefficients that encapsulate different definitions. Measurements may also be implemented differently. Not only do measurements differ; interconversion is impossible making comparisons challenging. There is a need to cull coefficients and for clear definitions of what precisely is meant by colocalisation in individual studies. Colocalisation can be considered to have two components; co-occurrence which reports whether the fluorophores are found together and correlation which reports on the similarity in their patterns of intensity.
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| 3. |
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| 4. |
- Ahlinder, Linnea, et al.
(author)
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Large Uptake of Titania and Iron Oxide Nanoparticles in the Nucleus of Lung Epithelial Cells as Measured by Raman Imaging and Multivariate Classification
- 2013
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In: Biophysical Journal. - : Elsevier BV. - 0006-3495 .- 1542-0086. ; 105:2, s. 310-319
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Journal article (peer-reviewed)abstract
- It is a challenging task to characterize the biodistribution of nanoparticles in cells and tissue on a subcellular level. Conventional methods to study the interaction of nanoparticles with living cells rely on labeling techniques that either selectively stain the particles or selectively tag them with tracer molecules. In this work, Raman imaging, a label-free technique that requires no extensive sample preparation, was combined with multivariate classification to quantify the spatial distribution of oxide nanoparticles inside living lung epithelial cells (A549). Cells were exposed to TiO2 (titania) and/or alpha-FeO(OH) (goethite) nanoparticles at various incubation times (4 or 48 h). Using multivariate classification of hyperspectral Raman data with partial least-squares discriminant analysis, we show that a surprisingly large fraction of spectra, classified as belonging to the cell nucleus, show Raman bands associated with nanoparticles. Up to 40% of spectra from the cell nucleus show Raman bands associated with nanoparticles. Complementary transmission electron microscopy data for thin cell sections qualitatively support the conclusions.
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| 5. |
- Ainla, Alar, 1982, et al.
(author)
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Lab on a Biomembrane
- 2014
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In: Biophysical Journal. - 0006-3495 .- 1542-0086. ; 106:2, s. 209A-209A
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Journal article (other academic/artistic)
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| 6. |
- Alizadehheidari, Mohammadreza, et al.
(author)
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Nanoconfined Circular DNA
- 2014
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In: Biophysical Journal. - : Elsevier BV. - 0006-3495 .- 1542-0086. ; 106:2, s. 274A-274A
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Journal article (other academic/artistic)abstract
- Nanofluidic channels have become a versatile tool to manipulate single DNA molecules. They allow investigation of confined single DNA molecules from a fundamental polymer physics perspective as well as for example in DNA barcoding techniques.
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| 7. |
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| 8. |
- Almqvist, Joachim E, 1980, et al.
(author)
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Modeling the Effect of Kv1.5 Block on the Canine Action Potential
- 2010
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In: Biophysical Journal. - : Elsevier BV. - 0006-3495 .- 1542-0086. ; 99:9, s. 2726-2736
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Journal article (peer-reviewed)abstract
- A wide range of ion channels have been considered as potential targets for pharmacological treatment of atrial fibrillation. The Kv1.5 channel, carrying the IKur current, has received special attention because it contributes to repolarization in the atria but is absent or weakly expressed in ventricular tissue. The dog serves as an important animal model for electrophysiological studies of the heart and mathematical models of the canine atrial action potential (CAAP) have been developed to study the interplay between ionic currents. To enable more-realistic studies on the effects of Kv1.5 blockers on the CAAP in silico, two continuous-time Markov models of the guarded receptor type were formulated for Kv1.5 and subsequently inserted into the Ramirez-Nattel-Courtemanche model of the CAAP. The main findings were: 1), time- and state-dependent Markov models of open-channel Kv1.5 block gave significantly different results compared to a time- and state-independent model with a downscaled conductance; 2), the outcome of Kv1.5 block on the macroscopic system variable APD90 was dependent on the precise mechanism of block; and 3), open-channel block produced a reverse use-dependent prolongation of APD90. This study suggests that more-complex ion-channel models are a prerequisite for quantitative modeling of drug effects.
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| 9. |
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| 10. |
- Andersson, Magnus, et al.
(author)
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Transport Pathway in Cu+ P-Type ATPases
- 2014
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In: Biophysical Journal. - : Elsevier BV. - 0006-3495 .- 1542-0086. ; 106:2, s. 427A-427A
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Journal article (other academic/artistic)
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