scholarly journals The role of traction in membrane curvature generation

2017 ◽  
Author(s):  
H. Alimohamadi ◽  
R. Vasan ◽  
J.E. Hassinger ◽  
J.C. Stachowiak ◽  
P. Rangamani
Keyword(s):  
Molecular Mechanisms ◽  
Unit Length ◽  
Line Tension ◽  
Membrane Curvature ◽  
Local Shape ◽  
Sources Of Uncertainty ◽  
Protein Scaffolding ◽  
Membrane Deformations ◽  
Membrane Shape

AbstractCurvature of biological membranes can be generated by a variety of molecular mechanisms including protein scaffolding, compositional heterogeneity, and cytoskeletal forces. These mechanisms have the net effect of generating tractions (force per unit length) on the bilayer that are translated into distinct shapes of the membrane. Here, we demonstrate how the local shape of the membrane can be used to infer the traction acting locally on the membrane. We show that buds and tubes, two common membrane deformations studied in trafficking processes, have different traction distributions along the membrane and that these tractions are specific to the molecular mechanism used to generate these shapes. Furthermore, we show that the magnitude of an axial force applied to the membrane as well as that of an effective line tension can be calculated from these tractions. Finally, we consider the sensitivity of these quantities with respect to uncertainties in material properties and follow with a discussion on sources of uncertainty in membrane shape.

scholarly journals The role of traction in membrane curvature generation

2018 ◽  
Vol 29 (16) ◽  
pp. 2024-2035 ◽  
Author(s):  
H. Alimohamadi ◽  
R. Vasan ◽  
J.E. Hassinger ◽  
J.C. Stachowiak ◽  
P. Rangamani
Keyword(s):  
Molecular Mechanisms ◽  
Unit Length ◽  
Line Tension ◽  
Membrane Curvature ◽  
Local Shape ◽  
Sources Of Uncertainty ◽  
Protein Scaffolding ◽  
Membrane Deformations ◽  
Membrane Shape

Curvature of biological membranes can be generated by a variety of molecular mechanisms including protein scaffolding, compositional heterogeneity, and cytoskeletal forces. These mechanisms have the net effect of generating tractions (force per unit length) on the bilayer that are translated into distinct shapes of the membrane. Here, we demonstrate how the local shape of the membrane can be used to infer the traction acting locally on the membrane. We show that buds and tubes, two common membrane deformations studied in trafficking processes, have different traction distributions along the membrane and that these tractions are specific to the molecular mechanism used to generate these shapes. Furthermore, we show that the magnitude of an axial force applied to the membrane as well as that of an effective line tension can be calculated from these tractions. Finally, we consider the sensitivity of these quantities with respect to uncertainties in material properties and follow with a discussion on sources of uncertainty in membrane shape.

scholarly journals Phosphatidic acid – a simple phospholipid with multiple faces

2018 ◽  
Vol 65 (2) ◽  
pp. 163-171 ◽  
Author(s):  
Jolanta Zegarlinska ◽  
Magda Piaścik ◽  
Aleksander F Sikorski ◽  
Aleksander Czogalla
Keyword(s):  
Phosphatidic Acid ◽  
Membrane Trafficking ◽  
Molecular Mechanisms ◽  
Gene Expression Regulation ◽  
Large Degree ◽  
Cellular Lipids ◽  
Living Organisms ◽  
Protein Recruitment ◽  
Membrane Shape

Phosphatidic acid (PA) is the simplest glycerophospholipid naturally occurring in living organisms, and even though its content among other cellular lipids is minor, it is drawing more and more attention due to its multiple biological functions. PA is a precursor for other phospholipids, acts as a lipid second messenger and, due to its structural properties, is also a modulator of membrane shape. Although much is known about interaction of PA with its effectors, the molecular mechanisms remain unresolved to a large degree. Throughout many of the well-characterized PA cellular sensors, no conserved binding domain can be recognized. Moreover, not much is known about the cellular dynamics of PA and how it is distributed among subcellular compartments. Remarkably, PA can play distinct roles within each of these compartments. For example, in the nucleus it behaves as a mitogen, influencing gene expression regulation, and in the Golgi membrane it plays a role in membrane trafficking. Here we discuss how a biophysical experimental approach enabled PA behavior to be described in the context of a lipid bilayer and to what extent various physicochemical conditions may modulate the functional properties of the lipid. Understanding these aspects would help to unravel specific mechanisms of PA-driven membrane transformation and protein recruitment and thus would lead to a clearer picture of the biological role of PA.

scholarly journals Developing Martini Coarse-Grained Nitrogen Gas Model for Lipid Nanobubble Simulations

2021 ◽  
Author(s):  
Fujia Tian ◽  
Xubo Lin
Keyword(s):  
Cell Membrane ◽  
Lipid Membranes ◽  
Molecular Mechanisms ◽  
Membrane Curvature ◽  
Dynamics Simulation ◽  
Coarse Grained ◽  
Atomistic Simulations ◽  
Nitrogen Gas ◽  
Hydrophobic Region

<p>By integrating the advantages of lipids’ biocompatibility and nanobubbles’ potent physicochemical properties, lipid nanobubbles show a great potential in ultrasound molecular imaging and biocompatible drug/gene delivery. However, under the interactions of the ultrasound, lipid nanobubbles may fuse with the cell membrane, changing the local membrane component and re-distributing encapsulated gas molecules into the hydrophobic region of the cell membrane, which may greatly affect the dynamics of certain membrane proteins and thus functions of cells. Although molecular dynamics simulation provides a useful computational tool to reveal the related molecular mechanisms, the lack of coarse-grained gas model greatly restricts this purpose. In the current work, we developed a Martini-compatible coarse-grained gas model based on the results of previous experiments and atomistic simulations, which could be used for lipid nanobubble simulations with complicated lipid components. By comparing the results of well-designed lipid nanobubble, lipid bi-monolayer and lipid bilayer simulations, we further revealed the role of membrane curvature and interleaflet coupling in the liquid-liquid phase separation of lipid membranes. It is worth mention that our developed coarse-grained nitrogen gas model can also be used for other gas-water interface systems such as pulmonary surfactant, which may overcome the possible artefacts arising from the usage of vacuum for gas phase. </p>

scholarly journals Developing Martini Coarse-Grained Nitrogen Gas Model for Lipid Nanobubble Simulations

2021 ◽  
Author(s):  
Fujia Tian ◽  
Xubo Lin
Keyword(s):  
Cell Membrane ◽  
Lipid Membranes ◽  
Molecular Mechanisms ◽  
Membrane Curvature ◽  
Dynamics Simulation ◽  
Coarse Grained ◽  
Atomistic Simulations ◽  
Nitrogen Gas ◽  
Hydrophobic Region

<p>By integrating the advantages of lipids’ biocompatibility and nanobubbles’ potent physicochemical properties, lipid nanobubbles show a great potential in ultrasound molecular imaging and biocompatible drug/gene delivery. However, under the interactions of the ultrasound, lipid nanobubbles may fuse with the cell membrane, changing the local membrane component and re-distributing encapsulated gas molecules into the hydrophobic region of the cell membrane, which may greatly affect the dynamics of certain membrane proteins and thus functions of cells. Although molecular dynamics simulation provides a useful computational tool to reveal the related molecular mechanisms, the lack of coarse-grained gas model greatly restricts this purpose. In the current work, we developed a Martini-compatible coarse-grained gas model based on the results of previous experiments and atomistic simulations, which could be used for lipid nanobubble simulations with complicated lipid components. By comparing the results of well-designed lipid nanobubble, lipid bi-monolayer and lipid bilayer simulations, we further revealed the role of membrane curvature and interleaflet coupling in the liquid-liquid phase separation of lipid membranes. It is worth mention that our developed coarse-grained nitrogen gas model can also be used for other gas-water interface systems such as pulmonary surfactant, which may overcome the possible artefacts arising from the usage of vacuum for gas phase. </p>

scholarly journals Martini Coarse-Grained Nitrogen Gas Model for Lipid Nanobubble Simulations

2021 ◽  
Author(s):  
Xubo Lin ◽  
Fujia Tian ◽  
Siewert-Jan Marrink
Keyword(s):  
Cell Membrane ◽  
Lipid Membranes ◽  
Molecular Mechanisms ◽  
Membrane Curvature ◽  
Dynamics Simulation ◽  
Coarse Grained ◽  
Atomistic Simulations ◽  
Nitrogen Gas ◽  
Hydrophobic Region

<p>By integrating the advantages of lipids’ biocompatibility and nanobubbles’ potent physicochemical properties, lipid nanobubbles show a great potential in ultrasound molecular imaging and biocompatible drug/gene delivery. However, under the interactions of the ultrasound, lipid nanobubbles may fuse with the cell membrane, changing the local membrane component and re-distributing encapsulated gas molecules into the hydrophobic region of the cell membrane, which may greatly affect the dynamics of certain membrane proteins and thus functions of cells. Although molecular dynamics simulation provides a useful computational tool to reveal the related molecular mechanisms, the lack of coarse-grained gas model greatly restricts this purpose. In the current work, we developed a Martini-compatible coarse-grained gas model based on the results of previous experiments and atomistic simulations, which could be used for lipid nanobubble simulations with complicated lipid components. By comparing the results of well-designed lipid nanobubble, lipid bi-monolayer and lipid bilayer simulations, we further revealed the role of membrane curvature and interleaflet coupling in the liquid-liquid phase separation of lipid membranes. It is worth mention that our developed coarse-grained nitrogen gas model can also be used for other gas-water interface systems such as pulmonary surfactant, which may overcome the possible artefacts arising from the usage of vacuum for gas phase. </p>

How do histone modifications contribute to transgenerational epigenetic inheritance in C. elegans?

2020 ◽  
Vol 48 (3) ◽  
pp. 1019-1034 ◽  
Author(s):  
Rachel M. Woodhouse ◽  
Alyson Ashe
Keyword(s):  
Histone Modifications ◽  
Molecular Mechanisms ◽  
Epigenetic Inheritance ◽  
Nematode Caenorhabditis Elegans ◽  
Histone Methyltransferases ◽  
Transgenerational Epigenetic Inheritance ◽  
C Elegans ◽  
Recent Developments ◽  
Gene Regulatory

Gene regulatory information can be inherited between generations in a phenomenon termed transgenerational epigenetic inheritance (TEI). While examples of TEI in many animals accumulate, the nematode Caenorhabditis elegans has proven particularly useful in investigating the underlying molecular mechanisms of this phenomenon. In C. elegans and other animals, the modification of histone proteins has emerged as a potential carrier and effector of transgenerational epigenetic information. In this review, we explore the contribution of histone modifications to TEI in C. elegans. We describe the role of repressive histone marks, histone methyltransferases, and associated chromatin factors in heritable gene silencing, and discuss recent developments and unanswered questions in how these factors integrate with other known TEI mechanisms. We also review the transgenerational effects of the manipulation of histone modifications on germline health and longevity.

Mesophyll conductance: the leaf corridors for photosynthesis

2020 ◽  
Vol 48 (2) ◽  
pp. 429-439 ◽  
Author(s):  
Jorge Gago ◽  
Danilo M. Daloso ◽  
Marc Carriquí ◽  
Miquel Nadal ◽  
Melanie Morales ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Main Role ◽  
Mesophyll Conductance ◽  
Future Studies ◽  
Cell Structures ◽  
Leaf Tissues ◽  
Change Framework ◽  
Chloroplast Stroma

Besides stomata, the photosynthetic CO2 pathway also involves the transport of CO2 from the sub-stomatal air spaces inside to the carboxylation sites in the chloroplast stroma, where Rubisco is located. This pathway is far to be a simple and direct way, formed by series of consecutive barriers that the CO2 should cross to be finally assimilated in photosynthesis, known as the mesophyll conductance (gm). Therefore, the gm reflects the pathway through different air, water and biophysical barriers within the leaf tissues and cell structures. Currently, it is known that gm can impose the same level of limitation (or even higher depending of the conditions) to photosynthesis than the wider known stomata or biochemistry. In this mini-review, we are focused on each of the gm determinants to summarize the current knowledge on the mechanisms driving gm from anatomical to metabolic and biochemical perspectives. Special attention deserve the latest studies demonstrating the importance of the molecular mechanisms driving anatomical traits as cell wall and the chloroplast surface exposed to the mesophyll airspaces (Sc/S) that significantly constrain gm. However, even considering these recent discoveries, still is poorly understood the mechanisms about signaling pathways linking the environment a/biotic stressors with gm responses. Thus, considering the main role of gm as a major driver of the CO2 availability at the carboxylation sites, future studies into these aspects will help us to understand photosynthesis responses in a global change framework.

The Role of the Endothelium in Premature Atherosclerosis: Molecular Mechanisms

2020 ◽  
Vol 27 (7) ◽  
pp. 1041-1051 ◽  
Author(s):  
Michael Spartalis ◽  
Eleftherios Spartalis ◽  
Antonios Athanasiou ◽  
Stavroula A. Paschou ◽  
Christos Kontogiannis ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Low Density Lipoprotein ◽  
Critical Role ◽  
Density Lipoprotein ◽  
Number Of Genes ◽  
Causes Of Mortality ◽  
Artery Disease ◽  
Genetic And Environmental Factors ◽  
Made In

Atherosclerotic disease is still one of the leading causes of mortality. Atherosclerosis is a complex progressive and systematic artery disease that involves the intima of the large and middle artery vessels. The inflammation has a key role in the pathophysiological process of the disease and the infiltration of the intima from monocytes, macrophages and T-lymphocytes combined with endothelial dysfunction and accumulated oxidized low-density lipoprotein (LDL) are the main findings of atherogenesis. The development of atherosclerosis involves multiple genetic and environmental factors. Although a large number of genes, genetic polymorphisms, and susceptible loci have been identified in chromosomal regions associated with atherosclerosis, it is the epigenetic process that regulates the chromosomal organization and genetic expression that plays a critical role in the pathogenesis of atherosclerosis. Despite the positive progress made in understanding the pathogenesis of atherosclerosis, the knowledge about the disease remains scarce.

E6 and E7 oncoproteins: Potential targets of cervical cancer

2020 ◽  
Vol 27 ◽  
Author(s):  
Ramarao Malla ◽  
Mohammad Amjad Kamal
Keyword(s):  
Cervical Cancer ◽  
Drug Resistance ◽  
Host Cell ◽  
Molecular Mechanisms ◽  
Immune Therapy ◽  
Cervical Lesions ◽  
Diagnostic Strategies ◽  
E6 And E7 Oncoproteins ◽  
E6 And E7

: Cervical cancer (CC) is the fourth leading cancer in women in the age group 15-44 globally. Experimental as well as epidemiological studies identified that type16 and 18 HPV cause 70% of precancerous cervical lesions as well as cervical cancer worldwide by bringing about genetic as well as epigenetic changes in the host genome. The insertion of the HPV genome triggers various defense mechanisms including the silencing of tumor suppressor genes as well as activation of oncogenes associated with cancer metastatic pathway. E6 and E7 are small oncoproteins consisting of 150 and 100 amino acids respectively. These oncoproteins affect the regulation of the host cell cycle by interfering with p53 and pRb. Further these oncoproteins adversely affect the normal functions of the host cell by binding to their signaling proteins. Recent studies demonstrated that E6 and E7 oncoproteins are potential targets for CC. Therefore, this review discusses the role of E6 and E7 oncoproteins in metastasis and drug resistance as well as their regulation, early oncogene mediated signaling pathways. This review also uncovers the recent updates on molecular mechanisms of E6 and E7 mediated phytotherapy, gene therapy, immune therapy, and vaccine strategies as well as diagnosis through precision testing. Therefore, understanding the potential role of E6/E7 in metastasis and drug resistance along with targeted treatment, vaccine, and precision diagnostic strategies could be useful for the prevention and treatment of cervical cancer.

NOB1: A Potential Biomarker or Target in Cancer

2019 ◽  
Vol 20 (10) ◽  
pp. 1081-1089
Author(s):  
Weiwei Ke ◽  
Zaiming Lu ◽  
Xiangxuan Zhao
Keyword(s):  
Cancer Treatment ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Binding Protein ◽  
Tumor Development ◽  
Anticancer Therapy ◽  
Research Progress ◽  
Normal Tissues ◽  
Potential Biomarker

Human NIN1/RPN12 binding protein 1 homolog (NOB1), an RNA binding protein, is expressed ubiquitously in normal tissues such as the lung, liver, and spleen. Its core physiological function is to regulate protease activities and participate in maintaining RNA metabolism and stability. NOB1 is overexpressed in a variety of cancers, including pancreatic cancer, non-small cell lung cancer, ovarian cancer, prostate carcinoma, osteosarcoma, papillary thyroid carcinoma, colorectal cancer, and glioma. Although existing data indicate that NOB1 overexpression is associated with cancer growth, invasion, and poor prognosis, the molecular mechanisms behind these effects and its exact roles remain unclear. Several studies have confirmed that NOB1 is clinically relevant in different cancers, and further research at the molecular level will help evaluate the role of NOB1 in tumors. NOB1 has become an attractive target in anticancer therapy because it is overexpressed in many cancers and mediates different stages of tumor development. Elucidating the role of NOB1 in different signaling pathways as a potential cancer treatment will provide new ideas for existing cancer treatment methods. This review summarizes the research progress made into NOB1 in cancer in the past decade; this information provides valuable clues and theoretical guidance for future anticancer therapy by targeting NOB1.

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