Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

On the use of in vivo cargo velocity as a biophysical marker.

ABSTRACT: Molecular motors move many intracellular cargos along microtubules. Recently, it has been hypothesized that in vivo cargo velocity can be used to determine the number of engaged motors. We use theoretical and experimental approaches to investigate these assertions, and find that this hypothesis is inconsistent with previously described motor behavior, surveyed and re-analyzed in this paper. Studying lipid droplet motion in Drosophila embryos, we compare transport in a mutant, Delta(halo), with that in wild-type embryos. The minus-end moving cargos in the mutant appear to be driven by more motors (based on in vivo stall force observations). Periods of minus-end motion are indeed longer than in wild-type embryos but the corresponding velocities are not higher. We conclude that velocity is not a definitive read-out of the number of motors propelling a cargo.

SUBMITTER: Martinez JE

PROVIDER: S-EPMC2889695 | biostudies-literature | 2007 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

On the use of in vivo cargo velocity as a biophysical marker.

Martinez Joel E JE Vershinin Michael D MD Shubeita George T GT Gross Steven P SP

Biochemical and biophysical research communications 20061222 3

Molecular motors move many intracellular cargos along microtubules. Recently, it has been hypothesized that in vivo cargo velocity can be used to determine the number of engaged motors. We use theoretical and experimental approaches to investigate these assertions, and find that this hypothesis is inconsistent with previously described motor behavior, surveyed and re-analyzed in this paper. Studying lipid droplet motion in Drosophila embryos, we compare transport in a mutant, Delta(halo), with t ...[more]

PMID: 17196170

Similar Datasets

Norms for Clinical Use of CXM, a Real-Time Marker of Height Velocity.

Project description:ContextHeight velocity (HV) is difficult to assess because growth is very slow. The current practice of calculating it from measurements taken at several-month intervals is insufficient for managing children with growth disorders. We identified a bone growth by-product (collagen X biomarker, CXM) in blood that in preliminary analysis in healthy children correlated strongly with conventionally determined HV and displayed a pattern resembling published norms for HV vs age.ObjectiveThe goal was to confirm our initial observations supporting the utility of CXM as an HV biomarker in a larger number of individuals and establish working reference ranges for future studies.Design, settings, and participantsCXM was assessed in archived blood samples from 302 healthy children and 10 healthy adults yielding 961 CXM measurements. A total of 432 measurements were plotted by age, and sex-specific reference ranges were calculated. Serial values from 116 participants were plotted against observed HV. Matched plasma, serum, and dried blood spot readings were compared.ResultsA correlation of blood CXM with conventional HV was confirmed. Scatter plots of CXM vs age showed a similar pattern to current HV norms, and CXM levels demarcated the pubertal growth spurt both in girls and boys. CXM levels differed little in matched serum, plasma, and dried blood spot samples.ConclusionsBlood CXM offers a potential means to estimate HV in real time. Our results establish sex-specific, working reference ranges for assessing skeletal growth, especially over time. CXM stability in stored samples makes it well suited for retrospective studies.

| S-EPMC7765635 | biostudies-literature

Biophysical Determinants and Constraints on Sperm Swimming Velocity.

Project description:Over the last 50 years, sperm competition has become increasingly recognised as a potent evolutionary force shaping male ejaculate traits. One such trait is sperm swimming speed, with faster sperm associated with increased fertilisation success in some species. Consequently, sperm are often thought to have evolved to be longer in order to facilitate faster movement. However, despite the intrinsic appeal of this argument, sperm operate in a different biophysical environment than we are used to, and instead increasing length may not necessarily be associated with higher velocity. Here, we test four predictive models (ConstantPower Density, Constant Speed, Constant Power Transfer, Constant Force) of the relationship between sperm length and speed. We collated published data on sperm morphology and velocity from 141 animal species, tested for structural clustering of sperm morphology and then compared the model predictions across all morphologically similar sperm clusters. Within four of five morphological clusters of sperm, we did not find a significant positive relationship between total sperm length and velocity. Instead, in four morphological sperm clusters we found evidence for the Constant Speed model, which predicts that power output is determined by the flagellum and so is proportional to flagellum length. Our results show the relationship between sperm morphology (size, width) and swimming speed is complex and that traditional models do not capture the biophysical interactions involved. Future work therefore needs to incorporate not only a better understanding of how sperm operate in the microfluid environment, but also the importance of fertilising environment, i.e., internal and external fertilisers. The microenvironment in which sperm operate is of critical importance in shaping the relationship between sperm length and form and sperm swimming speed.

| S-EPMC9656961 | biostudies-literature

Cytotoxic lymphocytes use mechanosurveillance to target biophysical vulnerabilities in cancer

Project description:Immune cells identify cancer cells by recognizing characteristic biochemical features indicative of oncogenic transformation. Cancer cells have characteristic mechanical features, as well, but whether these biophysical properties also contribute to destruction by the immune system is not known. In the present study, we found that enhanced expression of myocardin related transcription factors (MRTFs), which promote migration and metastatic invasion, paradoxically compromised lung colonization by melanoma and breast carcinoma cells in an immune-mediated manner. Cancer cells with increased MRTF signaling were also more sensitive to immune checkpoint blockade therapy in mice and humans. The basis for this vulnerability was not biochemical, but biophysical. MRTF expression strengthened the actin cytoskeleton, increasing the rigidity of cancer cells and thereby making them more vulnerable to cytotoxic T lymphocytes and natural killer cells. These results reveal a mechanical dimension of immunosurveillance, which we call mechanosurveillance, that is particularly relevant to the targeting of metastatic disease.

2021-04-01 | GSE164860 | GEO

Cell Adhesiveness Serves as a Biophysical Marker for Metastatic Potential.

Project description:Tumors are heterogeneous and composed of cells with different dissemination abilities. Despite significant effort, there is no universal biological marker that serves as a metric for metastatic potential of solid tumors. Common to disseminating cells from such tumors, however, is the need to modulate their adhesion as they detach from the tumor and migrate through stroma to intravasate. Adhesion strength is heterogeneous even among cancer cells within a given population, and using a parallel plate flow chamber, we separated and sorted these populations into weakly and strongly adherent groups; when cultured under stromal conditions, this adhesion phenotype was stable over multiple days, sorting cycles, and common across all epithelial tumor lines investigated. Weakly adherent cells displayed increased migration in both two-dimensional and three-dimensional migration assays; this was maintained for several days in culture. Subpopulations did not show differences in expression of proteins involved in the focal adhesion complex but did exhibit intrinsic focal adhesion assembly as well as contractile differences that resulted from differential expression of genes involved in microtubules, cytoskeleton linkages, and motor activity. In human breast tumors, expression of genes associated with the weakly adherent population resulted in worse progression-free and disease-free intervals. These data suggest that adhesion strength could potentially serve as a stable marker for migration and metastatic potential within a given tumor population and that the fraction of weakly adherent cells present within a tumor could act as a physical marker for metastatic potential. SIGNIFICANCE: Cancer cells exhibit heterogeneity in adhesivity, which can be used to predict metastatic potential.

| S-EPMC7024658 | biostudies-literature

A microscopy-based screen employing multiplex genome sequencing identifies cargo-specific requirements for dynein velocity.

Project description:The timely delivery of membranous organelles and macromolecules to specific locations within the majority of eukaryotic cells depends on microtubule-based transport. Here we describe a screening method to identify mutations that have a critical effect on intracellular transport and its regulation using mutagenesis, multicolor-fluorescence microscopy, and multiplex genome sequencing. This screen exploits the filamentous fungus Aspergillus nidulans, which has many of the advantages of yeast molecular genetics but uses long-range microtubule-based transport in a manner more similar to metazoan cells. Using this method, we identified seven mutants that represent novel alleles of components of the intracellular transport machinery: specifically, kinesin-1, cytoplasmic dynein, and the dynein regulators Lis1 and dynactin. The two dynein mutations identified in our screen map to dynein's AAA+ catalytic core. Single-molecule studies reveal that both mutations reduce dynein's velocity in vitro. In vivo these mutants severely impair the distribution and velocity of endosomes, a known dynein cargo. In contrast, another dynein cargo, the nucleus, is positioned normally in these mutants. These results reveal that different dynein functions have distinct stringencies for motor performance.

| S-EPMC3937092 | biostudies-literature

Force-velocity curves of motor proteins cooperating in vivo.

Project description:Motor proteins convert chemical energy into work, thereby generating persistent motion of cellular and subcellular objects. The velocities of motor proteins as a function of opposing loads have been previously determined in vitro for single motors. These single molecule "force-velocity curves" have been useful for elucidating motor kinetics and for estimating motor performance under physiological loads due to, for example, the cytoplasmic drag force on transported organelles. Here we report force-velocity curves for single and multiple motors measured in vivo. Using motion enhanced differential interference contrast (MEDIC) movies of living NT2 (neuron-committed teratocarcinoma) cells at 37 degrees C, three parameters were measured--velocity (v), radius (a), and effective cytoplasmic viscosity (eta')--as they applied to moving vesicles. These parameters were combined in Stokes' equation, F = 6piaeta'v, to determine the force, F, required to transport a single intracellular particle at velocity, v. In addition, the number of active motors was inferred from the multimodal pattern seen in a normalized velocity histogram. Using this inference, the resulting in vivo force-velocity curve for a single motor agrees with previously reported in vitro single motor force-velocity curves. Interestingly, however, the curves for two and three motors lie significantly higher in both measured velocity and computed force, which suggests that motors can work cooperatively to attain higher transport forces and velocities.

| S-EPMC2561921 | biostudies-literature

Cytotoxic lymphocytes use mechanosurveillance to target biophysical vulnerabilities in cancer

Project description:Cytotoxic lymphocytes use mechanosurveillance to target biophysical vulnerabilities in cancer

| PRJNA692218 | ENA

Atlatl use equalizes female and male projectile weapon velocity.

Project description:The atlatl is a handheld, rod-shaped device that employs leverage to launch a dart, and represents a major human technological innovation. One hypothesis for forager atlatl adoption over its presumed predecessor, the thrown javelin, is that a diverse array of people could achieve equal performance results, thereby facilitating inclusive participation of more people in hunting activities. We tested this hypothesis via a systematic assessment of 2160 weapon launch events by 108 people who used both technologies. Our results show that, unlike the javelin, the atlatl equalizes the velocity of female- and male-launched projectiles. This result indicates that a javelin to atlatl transition would have promoted a unification, rather than division, of labor. Moreover, our results suggest that female and male interments with atlatl weaponry should be interpreted similarly.

| S-EPMC10432391 | biostudies-literature

Cargo Delivery into the Brain by in vivo identified Transport Peptides.

Project description:The blood-brain barrier and the blood-cerebrospinal fluid barrier prevent access of biotherapeutics to their targets in the central nervous system and therefore prohibit the effective treatment of neurological disorders. In an attempt to discover novel brain transport vectors in vivo, we injected a T7 phage peptide library and continuously collected blood and cerebrospinal fluid (CSF) using a cisterna magna cannulated conscious rat model. Specific phage clones were highly enriched in the CSF after four rounds of selection. Validation of individual peptide candidates showed CSF enrichments of greater than 1000-fold. The biological activity of peptide-mediated delivery to the brain was confirmed using a BACE1 peptide inhibitor linked to an identified novel transport peptide which led to a 40% reduction of Amyloid-β in CSF. These results indicate that the peptides identified by the in vivo phage selection approach could be useful transporters for systemically administrated large molecules into the brain with therapeutic benefits.

| S-EPMC4585929 | biostudies-literature

Capillary-wall collagen as a biophysical marker of nanotherapeutic permeability into the tumor microenvironment.

Project description:The capillary wall is the chief barrier to tissue entry of therapeutic nanoparticles, thereby dictating their efficacy. Collagen fibers are an important component of capillary walls, affecting leakiness in healthy or tumor vasculature. Using a computational model along with in vivo systems, we compared how collagen structure affects the diffusion flux of a 1-nm chemotherapeutic molecule [doxorubicin (DOX)] and an 80-nm chemotherapy-loaded pegylated liposome (DOX-PLD) in tumor vasculature. We found a direct correlation between the collagen content around a tumor vessel to the permeability of that vessel permeability to DOX-PLD, indicating that collagen content may offer a biophysical marker of extravasation potential of liposomal drug formulations. Our results also suggested that while pharmacokinetics determined the delivery of DOX and DOX-PLD to the same tumor phenotype, collagen content determined the extravasation of DOX-PLD to different tumor phenotypes. Transport physics may provide a deeper view into how nanotherapeutics cross biological barriers, possibly helping explain the balance between biological and physical aspects of drug delivery.

| S-EPMC4134692 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data