Junction Network Research Articles

Synchronization-induced spike termination in networks of bistable neurons

We observe and study a self-organized phenomenon whereby the activity in a network of spiking neurons spontaneously terminates. We consider different types of populations, consisting of bistable model neurons connected electrically by gap junctions, or by either excitatory or inhibitory synapses, in a scale-free connection topology. We find that strongly synchronized population spiking events lead to complete cessation of activity in excitatory networks, but not in gap junction or inhibitory networks. We identify the underlying mechanism responsible for this phenomenon by examining the particular shape of the excitatory postsynaptic currents that arise in the neurons. We also examine the effects of the synaptic time constant, coupling strength, and channel noise on the occurrence of the phenomenon.

A Self-Regulating Gap Junction Network of Amacrine Cells Controls Nitric Oxide Release in the Retina

Neuromodulators regulate circuits throughout the nervous system, and revealing the cell types and stimulus conditions controlling their release is vital to understanding their function. The effects of the neuromodulator nitric oxide (NO) have been studied in many circuits, including in the vertebrate retina, where it regulates synaptic release, gap junction coupling, and blood vessel dilation, but little is known about the cells that release NO. We show that a single type of amacrine cell (AC) controls NO release in the inner retina, and we report its light responses, electrical properties, and calcium dynamics. We discover that this AC forms a dense gap junction network and that the strength of electrical coupling in the network is regulated by light through NO. A model of the network offers insights into the biophysical specializations leading to auto-regulation of NO release within the network.

Heat exposure affects jejunal tight junction remodeling independently of adenosine monophosphate-activated protein kinase in 9-day-old broiler chicks.

Dysfunction of the intestinal epithelial barrier under elevated temperatures is assumed to prompt pathological conditions and to eventually impede chickens' growth, resulting in massive economic losses in broiler industries. The aims of this research were to determine the impact of acute heat stress on the intestinal tight junction network of broiler chicks (Gallus domesticus L.) and to elucidate whether adenosine monophosphate-activated protein kinase (AMPK) was involved in the integrated response of the broiler's gastrointestinal tract to heat stress. A total of 80 9-day-old Arbor Acres chicks were subjected to temperature treatment (thermoneutral versus heat stress) and AMPK inhibition treatment (5mg/kg body weight intraperitoneal injection of compound C vs. sham treatment) for 72 h. In addition to monitoring growth performance, the mRNA and protein levels of key tight junction proteins, target components of the AMPK pathway, and biomarkers of intestinal inflammation and oxidative stress were assessed in the jejunum under both stressors at 24 and 72 h. An increase of the major tight junction proteins, claudin-1 and zonula occludens-1, was implemented in response to an exacerbated expression of the AMP-activated protein kinase. Heat stress did not affect zootechnical performance but was confirmed by an increased gene expression of heat shock proteins 70 and 90 as well as heat shock factor-1. In addition, hyperthermia induced significant effects on tight junction proteins, although it was independent of AMPK.

Macro scale modelling of cortical spreading depression and the role of astrocytic gap junctions

Neuronal activity evokes a localised increase in cerebral blood flow in a response known as neurovascular coupling (NVC), achieved through communication between a group of cells known as a neurovascular unit (NVU). Dysfunctional NVC can lead to pathologies such as cortical spreading depression (CSD), characterised by a slow moving wave of neuronal depolarisation and high extracellular K+ levels. This phenomenon can be affected by the presence of an astrocytic gap junction network which is able to transport K+ away from areas of high concentrations, however the precise role of these gap junctions remains controversial.In this study, a large scale numerical NVC model of a vascular tree coupled with multiple NVUs comprising a two-dimensional cerebral tissue slice is extended through extracellular K+ and Na+ electrodiffusion and K+ transport via an astrocytic gap junction network. An updated NVU model has been utilised that contains complex neuronal and extracellular dynamics and is able to simulate various pathologies such as CSD and the effect on the vascular response.Under pathological conditions (determined by model parameters) and with extracellular electrodiffusion the model is able to simulate a propagating wave of high extracellular K+ travelling at 6.7 mm/min as can occur in CSD. This wave travels outward from the neuronally stimulated area and is followed by a wave of vasoconstriction (with corresponding decreased blood flow) then slight vasodilation in agreement with multiple experimental results. The vasoconstrictive wave peaks after the K+ wave due to the delayed vascular response. Increasing the density of astrocytic gap junctions reduces the duration and amplitude of the vasoconstrictive wave and for high enough density the vasoconstrictive behaviour outside the stimulated area is eliminated. Gap junctions also reduce the area that is initially affected by vasoconstriction. This in silico model provides a complex and experimentally validated test bed for a variety of neurological phenomena.

A Cell Junctional Protein Network Associated with Connexin-26.

GJB2 mutations are the leading cause of non-syndromic inherited hearing loss. GJB2 encodes connexin-26 (CX26), which is a connexin (CX) family protein expressed in cochlea, skin, liver, and brain, displaying short cytoplasmic N-termini and C-termini. We searched for CX26 C-terminus binding partners by affinity capture and identified 12 unique proteins associated with cell junctions or cytoskeleton (CGN, DAAM1, FLNB, GAPDH, HOMER2, MAP7, MAPRE2 (EB2), JUP, PTK2B, RAI14, TJP1, and VCL) by using mass spectrometry. We show that, similar to other CX family members, CX26 co-fractionates with TJP1, VCL, and EB2 (EB1 paralogue) as well as the membrane-associated protein ASS1. The adaptor protein CGN (cingulin) co-immuno-precipitates with CX26, ASS1, and TJP1. In addition, CGN co-immunoprecipitation with CX30, CX31, and CX43 indicates that CX association is independent on the CX C-terminus length or sequence. CX26, CGN, FLNB, and DAMM1 were shown to distribute to the organ of Corti and hepatocyte plasma membrane. In the mouse liver, CX26 and TJP1 co-localized at the plasma membrane. In conclusion, CX26 associates with components of other membrane junctions that integrate with the cytoskeleton.

Light‐Stimulatable Molecules/Nanoparticles Networks for Switchable Logical Functions and Reservoir Computing

AbstractThe fabrication and electron transport properties of nanoparticles self‐assembled networks (NPSAN) of molecular switches (azobenzene derivatives) interconnected by Au nanoparticles are reported, and optically driven switchable logical operations associated to the light‐controlled switching of the molecules are demonstrated. The switching yield is up to 74%. It is also demonstrated that these NPSANs are prone to light‐stimulable reservoir computing. The complex nonlinearity of electron transport and dynamics in these highly connected and recurrent networks of molecular junctions exhibits rich high harmonics generation (HHG) required for reservoir computing approaches. Logical functions and HHG are controlled by the isomerization of the molecules upon light illumination. These results, without direct analogs in semiconductor devices, open new perspectives to molecular electronics in unconventional computing.

Abstract 402: Exclusion of Major Cell Types in the Murine Heart Enriches for Cardiac Pericytes

Cardiac fibrosis is one of the multitude of cardiac pathologies that occur in the event of acute myocardial injury and heart failure. Formation of scar tissue in the myocardium results in disrupted cardiomyocyte gap junction networks and reduced cardiac contractility. Cardiac pericytes are a heterogeneous population of mural cells that have been attributed to having a pro-fibrotic role in injury. However, due to the lack of specific markers for this cell, there has been difficulty in properly characterizing this population. We aimed to conduct single cell RNA-sequencing on this population to discover novel markers for cardiac pericytes and identify pro-fibrotic subpopulations that promote perivascular fibrosis. To avoid using current markers for cardiac pericytes, which lack specificity, we utilized an exclusion-based approach to enrich for the cardiac pericyte population in an unbiased manner. Using a combination of transgenic mice (αMHC GFP/+ ;Col1a1 GFP/+ ) and fluorescence-activated cell sorting (FACS), we excluded all major cardiac cell types, including cardiomyocytes, fibroblasts, endothelial cells, hematopoietic cells, smooth muscle cells, and cardiac neurons. We used Drop-sequencing technology to capture single cells and conducted RNA-sequencing. Cardiomyocytes (isolated by Langendorff), fibroblasts (FACS sorted Col1a1 + cells), endothelial cells (FACS sorted CD31 + cells), and smooth muscle cells (isolated from murine aortas) were also subjected to single-cell RNA-sequencing for comparison of gene expression profiles. Cells collected by the exclusion-based approach exhibited high expression of known pericyte markers and low expression of markers for other cell types. The t-SNE plots of all the populations revealed that the majority of cardiac pericytes shared similar gene expression profiles with smooth muscle cells while some cells clustered closer with fibroblasts. The use of an unbiased exclusion-based approach, coupled with single cell RNA-sequencing, allows for the identification of unique subpopulations of cardiac pericytes. Further investigation as to the functional roles of these cells will uncover potential therapeutic targets for treating cardiac fibrosis.

Mib1 prevents Notch Cis-inhibition to defer differentiation and preserve neuroepithelial integrity during neural delamination

The vertebrate neuroepithelium is composed of elongated progenitors whose reciprocal attachments ensure the continuity of the ventricular wall. As progenitors commit to differentiation, they translocate their nucleus basally and eventually withdraw their apical endfoot from the ventricular surface. However, the mechanisms allowing this delamination process to take place while preserving the integrity of the neuroepithelial tissue are still unclear. Here, we show that Notch signaling, which is classically associated with an undifferentiated state, remains active in prospective neurons until they delaminate. During this transition period, prospective neurons rapidly reduce their apical surface and only later down-regulate N-Cadherin levels. Upon Notch blockade, nascent neurons disassemble their junctions but fail to reduce their apical surface. This disrupted sequence weakens the junctional network and eventually leads to breaches in the ventricular wall. We also provide evidence that the Notch ligand Delta-like 1 (Dll1) promotes differentiation by reducing Notch signaling through a Cis-inhibition mechanism. However, during the delamination process, the ubiquitin ligase Mindbomb1 (Mib1) transiently blocks this Cis-inhibition and sustains Notch activity to defer differentiation. We propose that the fine-tuned balance between Notch Trans-activation and Cis-inhibition allows neuroepithelial cells to seamlessly delaminate from the ventricular wall as they commit to differentiation.

Self-reference, emotion inhibition and somatosensory disturbance: preliminary investigation of network perturbations in conversion disorder.

Conversion disorder (CD), or functional neurological disorder, is manifested as a neurological disturbance that is not macroscopically visible on clinical structural neuroimaging and is instead ascribed to underlying psychological stress. Known for many years in neuropsychiatry, a comprehensive explanation of the way in which psychological stress leads to a neurological deficit of a structural-like origin is still lacking. We applied whole-brain network-based data-driven analyses on resting-state functional magnetic resonance imaging, recorded in seven patients with acute-onset, stroke-like CD with unilateral paresis and hypoesthesia as compared with 15 age-matched healthy controls. We used a clustering analysis to measure functional connectivity (FC) strength within 10 different brain networks, as well as between these networks. Finally, we tested FC of specific brain regions that are known to be involved in CD. We found a significant increase in FC strength only within the default-mode network (DMN), which manages self-referential processing. Examination of inter-connectivity between networks showed a structure of disturbed connectivity, which included decreased connectivity between the DMN and limbic/salience network, increased connectivity between the limbic/salience network and body-related temporo-parieto-occipital junction network, decreased connectivity between the temporo-parieto-occipital junction and memory-related medial temporal lobe, and decreased connectivity between the medial temporal lobe and sensorimotor network. Region-specific FC analysis showed increased connectivity between the hippocampus and DMN. These preliminary results of disturbances in brain networks related to memory, emotions and self-referential processing, and networks involved in motor planning and execution, suggest a role of these cognitive functions in the psychopathology of CD.

Direct visualization of phase separation between superconducting and nematic domains in Co-doped CaFe2As2 close to a first-order phase transition

We show that biaxial strain induces alternating tetragonal superconducting and orthorhombic nematic domains in Co substituted CaFe2As2. We use Atomic Force, Magnetic Force and Scanning Tunneling Microscopy (AFM, MFM and STM) to identify the domains and characterize their properties, finding in particular that tetragonal superconducting domains are very elongated, more than several tens of micron long and about 30 nm wide, have the same Tc than unstrained samples and hold vortices in a magnetic field. Thus, biaxial strain produces a phase separated state, where each phase is equivalent to what is found at either side of the first order phase transition between antiferromagnetic orthorhombic and superconducting tetragonal phases found in unstrained samples when changing Co concentration. Having such alternating superconducting domains separated by normal conducting domains with sizes of order of the coherence length opens opportunities to build Josephson junction networks or vortex pinning arrays and suggests that first order quantum phase transitions lead to nanometric size phase separation under the influence of strain.

Characteristic of factors influencing the proper course of folliculogenesis in mammals

Abstract Folliculogenesis is the process of ovarian follicle formation,, taking presence during foetal period. During the follicular development, oogoniums undergo meiosis and oocytes are formed. In the ovaries of new born sows, primary and secondary follicles are present and, 90 days after birth, tertiary follicles appear. During development in the ovarian follicles growth of granulosa cells and differentiation of the thecal cells can be observed. A cavity filled with follicular fluid appears. Granulosa cells are divided into: mural cells and corona radiata, which together with the oocyte form the cumulus oophorus. Corona radiata cells, mural layers and oolemma contact each other by a network of gap junctions. Secreted from the pituitary gland, FSH and LH gonadotropin hormones act on receptors located in granular and follicular cells. In the postnatal life tertiary follicles and Graafian follicles are formed. When the follicle reaches a diameter of 1 mm, further growth depends on the secretion of gonadotropins. Mature ovarian follicles produce: progestins, androgens and oestrogens. The growth, differentiation and steroidogenic activity of ovarian follicles, in addition to FSH and LH, is also affected by prolactin, oxytocin, steroid and protein hormones, numerous proteins from the cytokine and interleukin family, metabolic hormones like insulin, glucocorticoids, leptin, thyroid hormones and growth hormones. Despite numerous studies, many processes related to folliculogenesis have not been discovered Learning the mechanisms regulating reproductive processes would allow to easily distinguish pathological processes and discover more and more genes and mechanisms of their expression in cells that build ovarian follicles.

Small Ca2+ releases enable hour-long high-frequency contractions in midshipman swimbladder muscle.

Type I males of the Pacific midshipman fish (Porichthys notatus) vibrate their swimbladder to generate mating calls, or "hums," that attract females to their nests. In contrast to the intermittent calls produced by male Atlantic toadfish (Opsanus tau), which occur with a duty cycle (calling time divided by total time) of only 3-8%, midshipman can call continuously for up to an hour. With 100% duty cycles and frequencies of 50-100 Hz (15°C), the superfast muscle fibers that surround the midshipman swimbladder may contract and relax as many as 360,000 times in 1 h. The energy for this activity is supported by a large volume of densely packed mitochondria that are found in the peripheral and central regions of the fiber. The remaining fiber cross section contains contractile filaments and a well-developed network of sarcoplasmic reticulum (SR) and triadic junctions. Here, to understand quantitatively how Ca2+ is managed by midshipman fibers during calling, we measure (a) the Ca2+ pumping-versus-pCa and force-versus-pCa relations in skinned fiber bundles and (b) changes in myoplasmic free [Ca2+] (Δ[Ca2+]) during stimulated activity of individual fibers microinjected with the Ca2+ indicators Mag-fluo-4 and Fluo-4. As in toadfish, the force-pCa relation in midshipman is strongly right-shifted relative to the Ca2+ pumping-pCa relation, and contractile activity is controlled in a synchronous, not asynchronous, fashion during electrical stimulation. SR Ca2+ release per action potential is, however, approximately eightfold smaller in midshipman than in toadfish. Midshipman fibers have a larger time-averaged free [Ca2+] during activity than toadfish fibers, which permits faster Ca2+ pumping because the Ca2+ pumps work closer to their maximum rate. Even with midshipman's sustained release and pumping of Ca2+, however, the Ca2+ energy cost of calling (per kilogram wet weight) is less than twofold more in midshipman than in toadfish.

One-Dimensional Particle Tracking with Streamline Preserving Junctions for Flows in Channel Networks

A pseudo-three-dimensional particle tracking model of drifter paths has been developed to study the movement of scalars through a complex network of tidal channels and junctions. To better simulate dispersion caused by bifurcation and merging at junctions, a localized model is proposed in which particles move along potential flow streamlines through junctions. The model is applied to the Sacramento–San Joaquin Delta in the California Central Valley, and the approach reproduces the observed ultimate fate of the endangered native fish Delta smelt more accurately than a model that fully randomizes particle positions at junctions. The new model also reproduces the very large dispersion that has been previously inferred from Delta-wide heat balances; this large dispersion appears to be associated with flow splits at junctions. Overall, the streamline-following model is likely to be more accurate for long-term planning and management simulations of such complex estuaries than more commonly used cross-sectionally averaged Lagrangian transport equation solvers, which randomize concentration distributions of scalars at junctions, and thereby do not reproduce the increased dispersion mechanisms.

Design of Miniaturized Triplexers via Sharing a Single Triple-Mode Cavity Resonator

A novel approach for design of a miniaturized cavity triplexer is proposed in this paper by using triple-mode resonator (TMR) as a common feeder of three frequency channels in a triplexer. Three frequency channels are generated by three fundamental modes of a single rectangular triple-mode cavity resonator. Without installing any connection-oriented junction network, i.e., T-junction or star junction, only coupling slots are adopted herein to achieve required coupling coefficients and external quality factors toward the specified Chebyshev responses in the three passbands simultaneously. High isolation among these three separated bands can be effectively achieved owing to the modal orthogonality via sharing a common TMR structure as a feeder. Two triplexers are then designed and fabricated using varied topologies. The hybrid resonator triplexer method is presented as the first approach by using a TMR as a feeder to feed three sets of single-mode cavity bandpass filters. As the second approach, the triple-mode triplexer (TMT) method is developed by cascading a few TMRs to form a multistage higher order TMT. Finally, two fabricated triplexer prototypes are tested for experimental verification of the proposed design methodology. Good agreement between measurement and simulation is achieved.

Modeling carrier density dependent charge transport in semiconducting carbon nanotube networks

Charge transport in a network of only semiconducting single-walled carbon nanotubes is modeled as a random-resistor network of tube-tube junctions. Solving Kirchhoff's current law with a numerical solver and taking into account the one-dimensional density of states of the nanotubes enables the evaluation of carrier density dependent charge transport properties such as network mobility, local power dissipation, and current distribution. The model allows us to simulate and investigate mixed networks that contain semiconducting nanotubes with different diameters, and thus different band gaps and conduction band edge energies. The obtained results are in good agreement with available experimental data.

State-Dependent Cross-Brain Information Flow in Borderline Personality Disorder

ImportanceAlthough borderline personality disorder (BPD)—one of the most common, burdensome, and costly psychiatric conditions—is characterized by repeated interpersonal conflict and instable relationships, the neurobiological mechanism of social interactive deficits remains poorly understood. ObjectiveTo apply recent advancements in the investigation of 2-person human social interaction to investigate interaction difficulties among people with BPD.Design, Setting, and ParticipantsCross-brain information flow in BPD was examined from May 25, 2012, to December 4, 2015, in pairs of participants studied in 2 linked functional magnetic resonance imaging scanners in a university setting. Participants performed a joint attention task. Each pair included a healthy control individual (HC) and either a patient currently fulfilling DSM-IV criteria for BPD (cBPD) (n = 23), a patient in remission for 2 years or more (rBPD) (n = 17), or a second HC (n = 20). Groups were matched for age and educational level. Main Outcomes and MeasuresA measure of cross-brain neural coupling was computed following previously published work to indicate synchronized flow between right temporoparietal junction networks (previously shown to host neural coupling abilities in health). This measure is derived from an independent component analysis contrasting the time courses of components between pairs of truly interacting participants compared with bootstrapped control pairs.ResultsIn the sample including 23 women with cBPD (mean [SD] age, 26.8 [5.7] years), 17 women with rBPD (mean [SD] age, 28.5 [4.3] years), and 80 HCs (mean [SD] age, 24.0 [3.4] years]) investigated as dyads, neural coupling was found to be associated with disorder state (η2 = 0.17; P = .007): while HC-HC pairs showed synchronized neural responses, cBPD-HC pairs exhibited significantly lower neural coupling just above permutation-based data levels (η2 = 0.16; P = .009). No difference was found between neural coupling in rBPD-HC and HC-HC pairs. The neural coupling in patients was significantly associated with childhood adversity (T = 2.3; P = .03).Conclusions and RelevanceThis study provides a neural correlate for a core diagnostic and clinical feature of BPD. Results indicate that hyperscanning may deliver state-associated biomarkers for clinical social neuroscience. In addition, at least some neural deficits of BPD may be more reversible than is currently assumed for personality disorders.

A simple cell transport device keeps culture alive and functional during shipping.

Transporting living complex cellular constructs through the mail while retaining their full viability and functionality is challenging. During this process, cells often suffer from exposure to suboptimal life-sustaining conditions (e.g. temperature, pH), as well as damage due to shear stress. We have developed a transport device for shipping intact cell/tissue constructs from one facility to another that overcomes these obstacles. Our transport device maintained three different cell lines (Caco2, A549, and HepG2 C3A) individually on transwell membranes with high viability (above 97%) for 48 h under simulated shipping conditions without an incubator. The device was also tested by actual overnight shipping of blood brain barrier constructs consisting of human induced pluripotent brain microvascular endothelial cells and rat astrocytes on transwell membranes to a remote facility (approximately 1200 miles away). The blood brain barrier constructs arrived with high cell viability and were able to regain full barrier integrity after equilibrating in the incubator for 24 h; this was assessed by the presence of continuous tight junction networks and in vivo-like values for trans-endothelial electrical resistance (TEER). These results demonstrated that our cell transport device could be a useful tool for long-distance transport of membrane-bound cell cultures and functional tissue constructs. Studies that involve various cell and tissue constructs, such as the "Multi-Organ-on-Chip" devices (where multiple microscale tissue constructs are integrated on a single microfluidic device) and studies that involve microenvironments where multiple tissue interactions are of interest, would benefit from the ability to transport or receive these constructs. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:1257-1266, 2017.

Heterogeneity of tight junctions in the thick ascending limb.

Renal tubular transport mechanisms are optimized to be energy efficient and tailored to local gradients and transport rates. The combined transcellular action of ion channels, transporters, and pumps, together with the paracellular pathway, enables kidney function. Monogenetic diseases and mouse models indicate that both trans- and paracellular proteins can become disease-causing candidates and may be targets for future therapeutic approaches. Recent advances in tight junction research have provided new insights into their structure, function, and regulation. The thick ascending limb (TAL) is a nephron segment with specific requirements for the paracellular pathway. It has to fuel the generation of the corticomedullary concentration gradient, to be watertight, and to provide a highly selective permeability for Na+ and divalent cations. Tight junction composition and function in the TAL is organized along the corticomedullary axis. Even on the level of a seemingly homogeneous tubular epithelium like the TAL, there is a separation of tight junction protein expression in the strands between the respective tricellular nexus of the junctional network. Here, we highlight some new insights from our recent work and that of others in this context. In addition, we provide some perspectives for the further study of paracellular transport mechanisms.

English

Shambu town has faced a problem of potable water supply, still large number of people did not have access to adequate amount of potable water and frequent water interruption is a common problem. The objective of this research was to evaluate the existing water pressure map and water demand. To achieve this goal, the following input data were collected, base population, growth rate, and pressure map of the area, water production data, and reservoir data. The pipe network and junction network system was simulated to understand its behavior for different inputs using EPANET 2.0. The results showed that the water pressure were not feasible enough to provide adequate water. Replacing the appropriate diameters to the distribution as well expanding the distribution network in necessary engagements, the total water demand was projected to be 567648 m3/year or 18 L/s and the total water supply was estimated to be 252288 m3/year or 8 L/s. Only 44% of the population was covered by water supply .Thus, use of ground water, or boreholes with an estimated yield of 8 L/s are to be drilled. Key words: EPANET, water demand, water supply, distribution network.

Actin cytoskeleton regulates functional anchorage-migration switch during T-cadherin-induced phenotype modulation of vascular smooth muscle cells

ABSTRACTVascular smooth muscle cell (SMC) switching between differentiated and dedifferentiated phenotypes is reversible and accompanied by morphological and functional alterations that require reconfiguration of cell-cell and cell-matrix adhesion networks. Studies attempting to explore changes in overall composition of the adhesion nexus during SMC phenotype transition are lacking. We have previously demonstrated that T-cadherin knockdown enforces SMC differentiation, whereas T-cadherin upregulation promotes SMC dedifferentiation. This study used human aortic SMCs ectopically modified with respect to T-cadherin expression to characterize phenotype-associated cell-matrix adhesion molecule expression, focal adhesions configuration and migration modes. Compared with dedifferentiated/migratory SMCs (expressing T-cadherin), the differentiated/contractile SMCs (T-cadherin-deficient) exhibited increased adhesion to several extracellular matrix substrata, decreased expression of several integrins, matrix metalloproteinases and collagens, and also distinct focal adhesion, adherens junction and intracellular tension network configurations. Differentiated and dedifferentiated phenotypes displayed distinct migrational velocity and directional persistence. The restricted migration efficiency of the differentiated phenotype was fully overcome by reducing actin polymerization with ROCK inhibitor Y-27632 whereas myosin II inhibitor blebbistatin was less effective. Migration efficiency of the dedifferentiated phenotype was diminished by promoting actin polymerization with lysophosphatidic acid. These findings held true in both 2D-monolayer and 3D-spheroid migration models. Thus, our data suggest that despite global differences in the cell adhesion nexus of the differentiated and dedifferentiated phenotypes, structural actin cytoskeleton characteristics per se play a crucial role in permissive regulation of cell-matrix adhesive interactions and cell migration behavior during T-cadherin-induced SMC phenotype transition.