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Publications (7 of 7) Show all publications
Krahn, N., Zhang, J., Melnikov, S. V., Tharp, J. M., Villa, A., Patel, A., . . . Söll, D. (2024). tRNA shape is an identity element for an archaeal pyrrolysyl-tRNA synthetase from the human gut. Nucleic Acids Research, 52(2), 513-524
Open this publication in new window or tab >>tRNA shape is an identity element for an archaeal pyrrolysyl-tRNA synthetase from the human gut
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2024 (English)In: Nucleic Acids Research, ISSN 0305-1048, E-ISSN 1362-4962, Vol. 52, no 2, p. 513-524Article in journal (Refereed) Published
Abstract [en]

Protein translation is orchestrated through tRNA aminoacylation and ribosomal elongation. Among the highly conserved structure of tRNAs, they have distinguishing features which promote interaction with their cognate aminoacyl tRNA synthetase (aaRS). These key features are referred to as identity elements. In our study, we investigated the tRNA:aaRS pair that installs the 22nd amino acid, pyrrolysine (tRNAPyl:PylRS). Pyrrolysyl-tRNA synthetases (PylRSs) are naturally encoded in some archaeal and bacterial genomes to acylate tRNAPyl with pyrrolysine. Their large amino acid binding pocket and poor recognition of the tRNA anticodon have been instrumental in incorporating >200 noncanonical amino acids. PylRS enzymes can be divided into three classes based on their genomic structure. Two classes contain both an N-terminal and C-terminal domain, however the third class (ΔpylSn) lacks the N-terminal domain. In this study we explored the tRNA identity elements for a ΔpylSn tRNAPyl from Candidatus Methanomethylophilus alvus which drives the orthogonality seen with its cognate PylRS (MaPylRS). From aminoacylation and translation assays we identified five key elements in ΔpylSn tRNAPyl necessary for MaPylRS activity. The absence of a base (position 8) and a G-U wobble pair (G28:U42) were found to affect the high-resolution structure of the tRNA, while molecular dynamic simulations led us to acknowledge the rigidity imparted from the G-C base pairs (G3:C70 and G5:C68).

Place, publisher, year, edition, pages
Oxford University Press (OUP), 2024
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:kth:diva-343199 (URN)10.1093/nar/gkad1188 (DOI)001126369700001 ()38100361 (PubMedID)2-s2.0-85183458735 (Scopus ID)
Note

QC 20240213

Available from: 2024-02-08 Created: 2024-02-08 Last updated: 2024-02-13Bibliographically approved
Majdolhosseini, M., Zhou, Z., Kleiven, S. & Villa, A. (2023). Which part of axonal membrane is the most vulnerable: A molecular dynamics/Finite Element study. European Biophysics Journal, 52(SUPPL 1), S39-S39
Open this publication in new window or tab >>Which part of axonal membrane is the most vulnerable: A molecular dynamics/Finite Element study
2023 (English)In: European Biophysics Journal, ISSN 0175-7571, E-ISSN 1432-1017, Vol. 52, no SUPPL 1, p. S39-S39Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
SPRINGER, 2023
National Category
Neurology
Identifiers
urn:nbn:se:kth:diva-335858 (URN)001029235400068 ()
Note

QC 20230911

Available from: 2023-09-11 Created: 2023-09-11 Last updated: 2023-09-11Bibliographically approved
Saeedimasine, M., Montanino, A., Kleiven, S. & Villa, A. (2021). Elucidating axonal injuries through molecular modelling of myelin sheaths and nodes of Ranvier. Frontiers in Molecular Biosciences, 8
Open this publication in new window or tab >>Elucidating axonal injuries through molecular modelling of myelin sheaths and nodes of Ranvier
2021 (English)In: Frontiers in Molecular Biosciences, E-ISSN 2296-889X, Vol. 8Article in journal (Refereed) Published
Place, publisher, year, edition, pages
Frontiers, 2021
National Category
Neurology Neurosciences Applied Mechanics
Identifiers
urn:nbn:se:kth:diva-297350 (URN)10.3389/fmolb.2021.669897 (DOI)000670062100001 ()34250015 (PubMedID)2-s2.0-85109141279 (Scopus ID)
Funder
Swedish Research Council, 2016-05314
Note

QC 20220426

Available from: 2021-06-14 Created: 2021-06-14 Last updated: 2022-06-25Bibliographically approved
Montanino, A., Saeedimasine, M., Villa, A. & Kleiven, S. (2019). Axons Embedded in a Tissue May Withstand Larger Deformations Than Isolated Axons Before Mechanoporation Occurs. Journal of Biomechanical Engineering, 141(12)
Open this publication in new window or tab >>Axons Embedded in a Tissue May Withstand Larger Deformations Than Isolated Axons Before Mechanoporation Occurs
2019 (English)In: Journal of Biomechanical Engineering, ISSN 0148-0731, E-ISSN 1528-8951, Vol. 141, no 12Article in journal (Refereed) Published
Abstract [en]

Diffuse axonal injury (DAI) is the pathological consequence of traumatic brain injury (TBI) that most of all requires a multiscale approach in order to be, first, understood and then possibly prevented. While in fact the mechanical insult usually happens at the head (or macro) level, the consequences affect structures at the cellular (or microlevel). The quest for axonal injury tolerances has so far been addressed both with experimental and computational approaches. On one hand, the experimental approach presents challenges connected to both temporal and spatial resolution in the identification of a clear axonal injury trigger after the application of a mechanical load. On the other hand, computational approaches usually consider axons as homogeneous entities and therefore are unable to make inferences about their viability, which is thought to depend on subcellular damages. Here, we propose a computational multiscale approach to investigate the onset of axonal injury in two typical experimental scenarios. We simulated single-cell and tissue stretch injury using a composite finite element axonal model in isolation and embedded in a matrix, respectively. Inferences on axonal damage are based on the comparison between axolemma strains and previously established mechanoporation thresholds. Our results show that, axons embedded in a tissue could withstand higher deformations than isolated axons before mechanoporation occurred and this is exacerbated by the increase in strain rate from 1/s to 10/s.

Place, publisher, year, edition, pages
ASME Press, 2019
Keywords
DAI, injury thresholds, mechanoporation, multiscale
National Category
Other Medical Engineering
Identifiers
urn:nbn:se:kth:diva-266763 (URN)10.1115/1.4044953 (DOI)000506878100014 ()31556941 (PubMedID)2-s2.0-85106256532 (Scopus ID)
Funder
Swedish National Infrastructure for Computing (SNIC), SNIC2017-1-491Swedish Research Council, VR-2016-05314
Note

QC 20200122

Available from: 2020-01-20 Created: 2020-01-20 Last updated: 2022-06-26Bibliographically approved
Saeedimasine, M., Montanino, A., Kleiven, S. & Villa, A. (2019). Role of lipid composition on the structural and mechanical features of axonal membranes: a molecular simulation study. Scientific Reports, 18, 27-39
Open this publication in new window or tab >>Role of lipid composition on the structural and mechanical features of axonal membranes: a molecular simulation study
2019 (English)In: Scientific Reports, E-ISSN 2045-2322, Vol. 18, p. 27-39Article in journal (Refereed) Published
Abstract [en]

The integrity of cellular membranes is critical for the functionality of axons. Failure of the axonal membranes (plasma membrane and/or myelin sheath) can be the origin of neurological diseases. The two membranes differ in the content of sphingomyelin and galactosylceramide lipids. We investigate the relation between lipid content and bilayer structural-mechanical properties, to better understand the dependency of membrane properties on lipid composition. A sphingomyelin/phospholipid/cholesterol bilayer is used to mimic a plasma membrane and a galactosylceramide/phospholipid/cholesterol bilayer to mimic a myelin sheath. Molecular dynamics simulations are performed at atomistic and coarse-grained levels to characterize the bilayers at equilibrium and under deformation. For comparison, simulations of phospholipid and phospholipid/cholesterol bilayers are also performed. The results clearly show that the bilayer biomechanical and structural features depend on the lipid composition, independent of the molecular models. Both galactosylceramide or sphingomyelin lipids increase the order of aliphatic tails and resistance to water penetration. Having 30% galactosylceramide increases the bilayers stiffness. Galactosylceramide lipids pack together via sugar-sugar interactions and hydrogen-bond phosphocholine with a correlated increase of bilayer thickness. Our findings provide a molecular insight on role of lipid content in natural membranes.

Place, publisher, year, edition, pages
Springer, 2019
National Category
Biochemistry and Molecular Biology
Research subject
Biological Physics
Identifiers
urn:nbn:se:kth:diva-252813 (URN)10.1038/s41598-019-44318-9 (DOI)000469318000013 ()31142762 (PubMedID)2-s2.0-85067054642 (Scopus ID)
Note

QC 20190613

Available from: 2019-06-10 Created: 2019-06-10 Last updated: 2024-03-18Bibliographically approved
Engin, O., Villa, A., Sayar, M. & Hess, B. (2010). Driving forces for adsorption of amphiphilic peptides to the air-water interface.. Journal of Physical Chemistry B, 114(34), 11093-11101
Open this publication in new window or tab >>Driving forces for adsorption of amphiphilic peptides to the air-water interface.
2010 (English)In: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 114, no 34, p. 11093-11101Article in journal (Refereed) Published
Abstract [en]

We have studied the partitioning of amphiphilic peptides at the air-water interface. The free energy of adsorption from bulk to interface was calculated by determining the potential of mean force via atomistic molecular dynamics simulations. To this end a method is introduced to restrain or constrain the center of mass of a group of molecules in a periodic system. The model amphiphilic peptides are composed of alternating valine and asparagine residues. The decomposition of the free energy difference between the bulk and interface is studied for different peptide block lengths. Our analysis revealed that for short amphiphilic peptides the surface driving force dominantly stems from the dehydration of hydrophobic side chains. The only opposing force is associated with the loss of orientational freedom of the peptide at the interface. For the peptides studied, the free energy difference scales linearly with the size of the molecule, since the peptides mainly adopt extended conformations both in bulk and at the interface. The free energy difference depends strongly on the water model, which can be rationalized through the hydration thermodynamics of hydrophobic solutes. Finally, we measured the reduction of the surface tension associated with complete coverage of the interface with peptides.

Keywords
Adsorption; Air; Dewatering; Free energy; Hydrophobicity; Molecular dynamics; Peptides; Surface tension
National Category
Physical Chemistry
Identifiers
urn:nbn:se:kth:diva-82659 (URN)10.1021/jp1024922 (DOI)000281128700020 ()20687527 (PubMedID)2-s2.0-77956083139 (Scopus ID)
Note
QC 20120215Available from: 2012-02-12 Created: 2012-02-12 Last updated: 2024-03-18Bibliographically approved
Montanino, A., Saeedimasine, M., Villa, A. & Kleiven, S. Localized axolemma deformations suggest mechanoporation as axonal injury trigger. Frontiers in Neurology
Open this publication in new window or tab >>Localized axolemma deformations suggest mechanoporation as axonal injury trigger
(English)In: Frontiers in Neurology, E-ISSN 1664-2295Article in journal (Refereed) Accepted
Abstract [en]

Traumatic brain injuries are a leading cause of morbidity and mortality worldwide. With almost 50% of traumatic brain injuries being related to axonal damage, understanding the nature of cellular level impairment is crucial. Experimental observations have so far led to the formulation of conflicting theories regarding the cellular primary injury mechanism. Disruption of the axolemma, or alternatively cytoskeletal damage has been suggested mainly as injury trigger. However, mechanoporation thresholds of generic membranes seem not to overlap with the axonal injury deformation range and microtubules appear too stiff and too weakly connected to undergo mechanical breaking. Here, we aim to shed a light on the mechanism of primary axonal injury, bridging finite element and molecular dynamics simulations. Despite the necessary level of approximation, our models can accurately describe the mechanical behavior of the unmyelinated axon and its membrane. More importantly, they give access to quantities that would be inaccessible with an experimental approach. We show that in a typical injury scenario, the axonal cortex sustains deformations large enough to entail pore formation in the adjoining lipid bilayer. The observed axonal deformation of 10-12% agree well with the thresholds proposed in the literature for axonal injury and, above all, allow us to provide quantitative evidences that do not exclude pore formation in the membrane as a result of trauma. Our findings bring to an increased knowledge of axonal injury mechanism that will have positive implications for the prevention and treatment of brain injuries.

Keywords
mechanoporation, axolemma, axonal injury, Membrane Permeability, Traumatic Brain Injury, Finite Element
National Category
Other Medical Engineering
Research subject
Medical Technology; Biological Physics; Solid Mechanics; Technology and Health
Identifiers
urn:nbn:se:kth:diva-266761 (URN)10.3389/fneur.2020.00025 (DOI)000514906900001 ()2-s2.0-85079505686 (Scopus ID)
Funder
Swedish Research Council, VR- Q13 2016-05314
Note

QCR 20200122

Available from: 2020-01-20 Created: 2020-01-20 Last updated: 2023-08-28Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-9573-0326

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