34 research outputs found
Tubulin bond energies and microtubule biomechanics determined from nanoindentation in silico
Microtubules, the primary components of the chromosome segregation machinery,
are stabilized by longitudinal and lateral non-covalent bonds between the
tubulin subunits. However, the thermodynamics of these bonds and the
microtubule physico-chemical properties are poorly understood. Here, we explore
the biomechanics of microtubule polymers using multiscale computational
modeling and nanoindentations in silico of a contiguous microtubule fragment. A
close match between the simulated and experimental force-deformation spectra
enabled us to correlate the microtubule biomechanics with dynamic structural
transitions at the nanoscale. Our mechanical testing revealed that the
compressed MT behaves as a system of rigid elements interconnected through a
network of lateral and longitudinal elastic bonds. The initial regime of
continuous elastic deformation of the microtubule is followed by the transition
regime, during which the microtubule lattice undergoes discrete structural
changes, which include first the reversible dissociation of lateral bonds
followed by irreversible dissociation of the longitudinal bonds. We have
determined the free energies of dissociation of the lateral (6.9+/-0.4
kcal/mol) and longitudinal (14.9+/-1.5 kcal/mol) tubulin-tubulin bonds. These
values in conjunction with the large flexural rigidity of tubulin
protofilaments obtained (18,000-26,000 pN*nm^2), support the idea that the
disassembling microtubule is capable of generating a large mechanical force to
move chromosomes during cell division. Our computational modeling offers a
comprehensive quantitative platform to link molecular tubulin characteristics
with the physiological behavior of microtubules. The developed in silico
nanoindentation method provides a powerful tool for the exploration of
biomechanical properties of other cytoskeletal and multiprotein assemblie
Assessment of exposure to Plasmodium falciparum transmission in a low endemicity area by using multiplex fluorescent microsphere-based serological assays
Background: The evaluation of malaria transmission intensity is a crucial indicator for estimating the burden of malarial disease. In this respect, entomological and parasitological methods present limitations, especially in low transmission areas. The present study used a sensitive multiplex assay to assess the exposure to Plasmodium falciparum infection in children living in an area of low endemicity. In three Senegalese villages, specific antibody (IgG) responses to 13 pre-erythrocytic P. falciparum peptides derived from Lsa1, Lsa3, Glurp, Salsa, Trap, Starp, Csp and Pf11.1 proteins were simultaneously evaluated before (June), at the peak (September) and after (December) the period of malaria transmission, in children aged from 1 to 8 years. Results: Compared to other antigens, a high percentage of seropositivity and specific antibody levels were detected with Glurp, Salsa1, Lsa3NR2, and Lsa1J antigens. The seropositivity increased with age for all tested antigens. Specific IgG levels to Glurp, Salsa1, Lsa3NR2, and Lsa1J were significantly higher in P. falciparum infected children compared to non-infected and this increase is significantly correlated with parasite density. Conclusion: The multiplex assay represents a useful technology for a serological assessment of rapid variations in malaria transmission intensity, especially in a context of low parasite rates. The use of such combined serological markers (i.e. Glurp, Lsa1, Lsa3, and Salsa) could offer the opportunity to examine these variations over time, and to evaluate the efficacy of integrated malaria control strategies
Growth Mindset as a Student Support Tool during a Pandemic
Supporting students in their learning is important at
any time
but especially so during the Covid-19 pandemic. One way to help students
feel supported is to encourage them to develop a growth mindset for
their learning. In this paper, we present data collected during the
Fall 2020 to Spring 2022 semesters from a general biochemistry course,
where frequent short activities were completed to help students foster
a growth mindset. Survey responses indicate that 73.6% of all students
felt they had more of a growth mindset at the end of the course compared
to only 29.6% of students knowing about growth mindset before the
class. Further, the fact that the start of the semester activities
were rated the most helpful by students shows a need for early, and
even the first day of class, interventions on growth mindset
Multiscale Modeling of the Nanomechanics of Microtubule Protofilaments
Large-size biomolecular systems that spontaneously assemble,
disassemble,
and self-repair by controlled inputs play fundamental roles in biology.
Microtubules (MTs), which play important roles in cell adhesion and
cell division, are a prime example. MTs serve as ″tracks″
for molecular motors, and their biomechanical functions depend on
dynamic instabilitya stochastic switching between periods
of rapid growing and shrinking. This process is controlled by many
cellular factors so that growth and shrinkage periods are correlated
with the life cycle of a cell. Resolving the molecular basis for the
action of these factors is of paramount importance for understanding
the diverse functions of MTs. We employed a multiscale modeling approach
to study the force-induced MT depolymerization by analyzing the mechanical
response of a MT protofilament to external forces. We carried out
self-organized polymer (SOP) model based simulations accelerated on
Graphics Processing Units (GPUs). This approach enabled us to follow
the mechanical behavior of the molecule on experimental time scales
using experimental force loads. We resolved the structural details
and determined the physical parameters that characterize the stretching
and bending modes of motion of a MT protofilament. The central result
is that the severing action of proteins, such as katanin and kinesin,
can be understood in terms of their mechanical coupling to a protofilament.
For example, the extraction of tubulin dimers from MT caps by katanin
can be achieved by pushing the protofilament toward the axis of the
MT cylinder, while the removal of large protofilaments curved into
″ram’s horn″ structures by kinesin is the result
of the outward bending of the protofilament. We showed that, at the
molecular level, these types of deformations are due to the anisotropic,
but homogeneous, micromechanical properties of MT protofilaments
Tubulin Bond Energies and Microtubule Biomechanics Determined from Nanoindentation <i>in Silico</i>
Microtubules,
the primary components of the chromosome segregation
machinery, are stabilized by longitudinal and lateral noncovalent
bonds between the tubulin subunits. However, the thermodynamics of
these bonds and the microtubule physicochemical properties are poorly
understood. Here, we explore the biomechanics of microtubule polymers
using multiscale computational modeling and nanoindentations <i>in silico</i> of a contiguous microtubule fragment. A close
match between the simulated and experimental force–deformation
spectra enabled us to correlate the microtubule biomechanics with
dynamic structural transitions at the nanoscale. Our mechanical testing
revealed that the compressed MT behaves as a system of rigid elements
interconnected through a network of lateral and longitudinal elastic
bonds. The initial regime of continuous elastic deformation of the
microtubule is followed by the transition regime, during which the
microtubule lattice undergoes discrete structural changes, which include
first the reversible dissociation of lateral bonds followed by irreversible
dissociation of the longitudinal bonds. We have determined the free
energies of dissociation of the lateral (6.9 ± 0.4 kcal/mol)
and longitudinal (14.9 ± 1.5 kcal/mol) tubulin–tubulin
bonds. These values in conjunction with the large flexural rigidity
of tubulin protofilaments obtained (18,000–26,000 pN·nm<sup>2</sup>) support the idea that the disassembling microtubule is capable
of generating a large mechanical force to move chromosomes during
cell division. Our computational modeling offers a comprehensive quantitative
platform to link molecular tubulin characteristics with the physiological
behavior of microtubules. The developed <i>in silico</i> nanoindentation method provides a powerful tool for the exploration
of biomechanical properties of other cytoskeletal and multiprotein
assemblies
Tubulin Bond Energies and Microtubule Biomechanics Determined from Nanoindentation <i>in Silico</i>
Microtubules,
the primary components of the chromosome segregation
machinery, are stabilized by longitudinal and lateral noncovalent
bonds between the tubulin subunits. However, the thermodynamics of
these bonds and the microtubule physicochemical properties are poorly
understood. Here, we explore the biomechanics of microtubule polymers
using multiscale computational modeling and nanoindentations <i>in silico</i> of a contiguous microtubule fragment. A close
match between the simulated and experimental force–deformation
spectra enabled us to correlate the microtubule biomechanics with
dynamic structural transitions at the nanoscale. Our mechanical testing
revealed that the compressed MT behaves as a system of rigid elements
interconnected through a network of lateral and longitudinal elastic
bonds. The initial regime of continuous elastic deformation of the
microtubule is followed by the transition regime, during which the
microtubule lattice undergoes discrete structural changes, which include
first the reversible dissociation of lateral bonds followed by irreversible
dissociation of the longitudinal bonds. We have determined the free
energies of dissociation of the lateral (6.9 ± 0.4 kcal/mol)
and longitudinal (14.9 ± 1.5 kcal/mol) tubulin–tubulin
bonds. These values in conjunction with the large flexural rigidity
of tubulin protofilaments obtained (18,000–26,000 pN·nm<sup>2</sup>) support the idea that the disassembling microtubule is capable
of generating a large mechanical force to move chromosomes during
cell division. Our computational modeling offers a comprehensive quantitative
platform to link molecular tubulin characteristics with the physiological
behavior of microtubules. The developed <i>in silico</i> nanoindentation method provides a powerful tool for the exploration
of biomechanical properties of other cytoskeletal and multiprotein
assemblies