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Kazmierczak, B.

Publications and source records attributed to Kazmierczak, B..

4 recordsLinked to original sources

Modeling Fast CICI Calcium Waves

Following the suggestion of L. F. Jaffe [1] we propose a mathematical model of fast calcium induced calcium influx waves (CICI Waves). They can propagate at relatively high speeds (up to 1300 micrometers/s). According to [1], they propagate due to a mechanochemical interaction of actomyosin network with the cell membrane. The local stretching of the membrane caused by actin filaments opens mechanically operated ion channels resulting in the influx of calcium to the cell. Moreover, stretching a cells membrane at one point opens nearby stretch activated calcium channels because the mechanical force is relayed by the actin filaments interconnected by myosin bridges. The number of bridges as well as filament density increases with calcium concentration, causing the contraction of the actomyosin network. Thus, the force acting on the membrane from tangled actin filaments is transmitted ahead of the moving front of the calcium concentration. As a result, the ion channels are opened even before the signal of calcium reaches them. This leads to much larger propagation speed of CICI waves in comparison with calcium induced calcium released (CICR) waves, where the wave is sustained by the diffusion of calcium and autocatalytic release of calcium from the internal stores (e.g. endoplasmic reticula).

physiology↗

Mathematical modelling of tissue growth control by a negative feedback

This study investigates the regulation of tissue growth through mathematical modeling of systemic and local feedback mechanisms. Employing reaction-diffusion equations, the models explore the dynamics of tissue growth, emphasizing endocrine signaling and inter-tissue communication. The analysis identifies critical factors influencing the emergence of spatial structures, bifurcation phenomena, the existence and stability of stationary pulse and wave solutions. It also elucidates mechanisms for achieving coordinated tissue growth. In particular, if negative feedback is sufficiently strong, their final finite size is provided by a stable pulse, otherwise they manifest unlimited growth in the form of a wave. These findings contribute to the theoretical insights into biological processes such as embryogenesis, regeneration, and tumor development, while highlighting the role of feedback systems in maintaining physiological homeostasis.

developmental biology↗

Modeling the bistable transition between cell phenotypes during limb precartilage condensation

The tetrapod limb skeleton is initiated in unpatterned limb bud mesenchyme by the formation of precartilage condensations. Here, based on time-lapse videographic analysis of a forming condensation in a high-density culture of chicken limb bud mesenchyme, we observe a phase transition to a more fluidized state for cells within spatial compacted foci (protocondensations that will progress to condensations), as reflected in their spatial confinement, cell-substratum interaction and speed of motion. Previous work showed that galectin-8 and galectin-1A, two proteins of the galactoside-binding galectin family, are the earliest determinants of this process in the chicken limb bud, and that their interactions in forming skeletogenic patterns of condensations can be interpreted mathematically through a reaction-diffusion-adhesion framework. Based on this framework, we use an ordinary differential equation-based approach to analyze the core switching modality of the galectin reaction network and characterize the states of the network independent of the diffusive and adhesive arms of the patterning mechanism. We identify two steady states where the concentrations of both galectins are respectively, negligible, and very high. An explicit Lyapunov function shows that there are no periodic solutions. For sigmoidal galectin production terms, the model exhibits a bistable switch that arises from a monostable state via saddle-node bifurcation. Our model therefore predicts that the galectin network exists in low and high expression states separated in space or time without any intermediate states. This provides a causal basis for the observed outside vs. inside transition observed in the in vitro video data. We performed a quantitative analysis of the distribution of galectin-1A in cultures of condensing chick limb mesenchymal cells and found that the interior of the protocondensations had concentrations of this protein (compared to the immediate exterior) over and above that expected from its higher cell density, consistent with the models predictions. The galectin-based patterning network is thus suggested, on theoretical grounds, to incorporate a core switch independent of any spatial or temporal dynamics, that drives the chondrogenic cell state transition in limb skeletogenesis.

developmental biology↗

Modulation of Flagellar Rotation in Surface-Attached Bacteria: A Circuit for Rapid Surface-Sensing

Attachment is a necessary first step in bacterial commitment to surface-associated behaviors that include colonization, biofilm formation, and host-directed virulence. The Gram-negative opportunistic pathogen Pseudomonas aeruginosa can initially attach to surfaces via its single polar flagellum. Although many bacteria quickly detach, some become irreversibly attached and express surface-associated structures, such as Type IV pili, and behaviors, including twitching motility and biofilm initiation. P. aeruginosa that lack the GTPase FlhF assemble a randomly placed flagellum that is motile; however, we observed that these mutant bacteria show defects in biofilm formation comparable to those seen for non-motile, aflagellate bacteria. This phenotype was associated with altered behavior of {Delta}flhF bacteria immediately following surface-attachment. Forward and reverse genetic screens led to the discovery that FlhF interacts with FimV to control flagellar rotation at a surface, and implicated cAMP signaling in this pathway. Although cAMP controls many transcriptional programs in P. aeruginosa, the known targets of this second messenger were not required to modulate flagellar rotation in surface-attached bacteria. Instead, alterations in switching behavior of the motor appear to result from previously undescribed effects of cAMP on switch complex proteins and/or the motor-stators associated with them.\n\nAuthor SummaryAttachment to a surface often triggers programs of gene expression that alter the behavior, virulence and fitness of bacteria. Initial contact is usually mediated by surface exposed adhesins, such as flagella or pili/fimbriae, and there is much interest in how these structures might sense and respond to surface attachment. The human bacterial pathogen Pseudomonas aeruginosa usually contacts surfaces via its polar flagellum, the rotary motor that also powers bacterial swimming. We observed that wild-type bacteria quickly stopped rotating their flagellum after surface attachment, but that a mutant lacking the flagellar-associated protein FlhF did not. Using a combination of genetic approaches, we demonstrated that FlhF interacts with a component of the flagellar rotor (FliG) and with a polar scaffolding protein that positively regulates cAMP production (FimV) to stop flagellar rotation and thereby favor bacterial persistence at a surface. We provide evidence that the second messenger cAMP is the likely signal generated by flagellar-mediated surface attachment and show that cAMP is sufficient to alter the behavior of the flagellar motor.

microbiology↗