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1. Flagellum-driven motility enhances Pseudomonas aeruginosa biofilm formation by altering cell orientation

   https://doi.org/10.1128/aem.00821-25  

   Wei, Guanju; Palalay, Jessica-Jae S; Sanfilippo, Joseph E; Yang, Judy Q (July 2025, Applied and Environmental Microbiology)

   van_Kessel, Julia C (Ed.)

   ABSTRACT Bacterial motility plays a crucial role in biofilm development, yet the underlying mechanism remains not fully understood. Here, we demonstrate that the flagellum-driven motility ofPseudomonas aeruginosaenhances biofilm formation by altering the orientation of bacterial cells, an effect controlled by shear stress rather than shear rate. By tracking wild-typeP. aeruginosaand its non-motile mutants in a microfluidic channel, we demonstrate that while non-motile cells align with the flow, many motile cells can orient toward the channel sidewalls, enhancing cell surface attachment and increasing biofilm cell density by up to 10-fold. Experiments with varying fluid viscosities further demonstrate that bacterial swimming speed decreases with increasing fluid viscosity, and the cell orientation scales with the shear stress rather than shear rate. Our results provide a quantitative framework to predict the role of motility in the orientation and biofilm development under different flow conditions and viscosities.IMPORTANCEBiofilms are ubiquitous in rivers, water pipes, and medical devices, impacting the environment and human health. While bacterial motility plays a crucial role in biofilm development, a mechanistic understanding remains limited, hindering our ability to predict and control biofilms. Here, we reveal how the motility ofPseudomonas aeruginosa, a common pathogen, influences biofilm formation through systematically controlled microfluidic experiments with confocal and high-speed microscopy. We demonstrate that the orientation of bacterial cells is controlled by shear stress. While non-motile cells primarily align with the flow, many motile cells overcome the fluid shear forces and reorient toward the channel sidewalls, increasing biofilm cell density by up to 10-fold. Our findings provide insights into how bacterial transition from free-swimming to surface-attached states under varying flow conditions, emphasizing the role of cell orientation in biofilm establishment. These results enhance our understanding of bacterial behavior in flow environments, informing strategies for biofilm management and control. 

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2. Advances in sensor developments for cell culture monitoring

   https://doi.org/10.1002/bmm2.12047  

   Kim, Ka Ram; Yeo, Woon‐Hong (September 2023, BMEMat)

   Abstract Cell culture encompasses procedures for extracting cells from their natural tissue and cultivating them under controlled artificial conditions. During this process, various factors, including cell physiological/morphological properties, culture environments, metabolites, and contaminants, have to be precisely controlled and monitored for the survival of cells and the pursuit of the desired properties of the cells. This review summarizes recent advances in sensor technologies and manufacturing strategies for various cell culture platforms using traditional plastics, microfluidic chips, and scalable bioreactors. We share the details of newly developed biological sensors, chemical sensors, optical sensors, electronic chip technologies, and material integration methods. The precise control of parameters based on the feedback by these sensors and electronics enhances cell culture quality and throughput. 

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3. Electronic profiling of membrane antigen expression via immunomagnetic cell manipulation

   https://doi.org/10.1039/c9lc00297a  

   Civelekoglu, Ozgun; Wang, Ningquan; Boya, Mert; Ozkaya-Ahmadov, Tevhide; Liu, Ruxiu; Sarioglu, A. Fatih (January 2019, Lab on a Chip)

   Membrane antigens control cell function by regulating biochemical interactions and hence are routinely used as diagnostic and prognostic targets in biomedicine. Fluorescent labeling and subsequent optical interrogation of cell membrane antigens, while highly effective, limit expression profiling to centralized facilities that can afford and operate complex instrumentation. Here, we introduce a cytometry technique that computes surface expression of immunomagnetically labeled cells by electrically tracking their trajectory under a magnetic field gradient on a microfluidic chip with a throughput of >500 cells per min. In addition to enabling the creation of a frugal cytometry platform, this immunomagnetic cell manipulation-based measurement approach allows direct expression profiling of target subpopulations from non-purified samples. We applied our technology to measure epithelial cell adhesion molecule expression on human breast cancer cells. Once calibrated, surface expression and size measurements match remarkably well with fluorescence-based measurements from a commercial flow cytometer. Quantitative measurements of biochemical and biophysical cell characteristics with a disposable cytometer have the potential to impact point of care testing of clinical samples particularly in resource limited settings. 

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4. Mechanical interaction between a hydrogel and an embedded cell in biomicrofluidic applications

   https://doi.org/10.1063/5.0263344  

   Li, Lei; Zhang, Jiaqi; Yue, Pengtao; Feng, James J (March 2025, Biomicrofluidics)

   Thanks to their softness, biocompatibility, porosity, and ready availability, hydrogels are commonly used in microfluidic assays and organ-on-chip devices as a matrix for cells. They not only provide a supporting scaffold for the differentiating cells and the developing organoids, but also serve as the medium for transmitting oxygen, nutrients, various chemical factors, and mechanical stimuli to the cells. From a bioengineering viewpoint, the transmission of forces from fluid perfusion to the cells through the hydrogel is critical to the proper function and development of the cell colony. In this paper, we develop a poroelastic model to represent the fluid flow through a hydrogel containing a biological cell modeled as a hyperelastic inclusion. In geometries representing shear and normal flows that occur frequently in microfluidic experiments, we use finite-element simulations to examine how the perfusion engenders interstitial flow in the gel and displaces and deforms the embedded cell. The results show that pressure is the most important stress component in moving and deforming the cell, and the model predicts the velocity in the gel and stress transmitted to the cell that is comparable to in vitro and in vivo data. This work provides a computational tool to design the geometry and flow conditions to achieve optimal flow and stress fields inside the hydrogels and around the cell. 

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5. Stability and deformation of biomolecular condensates under the action of shear flow

   https://doi.org/10.1063/5.0209119  

   Coronas, Luis E; Van, Thong; Iorio, Antonio; Lapidus, Lisa J; Feig, Michael; Sterpone, Fabio (June 2024, The Journal of Chemical Physics)

   Biomolecular condensates play a key role in cytoplasmic compartmentalization and cell functioning. Despite extensive research on the physico-chemical, thermodynamic, or crowding aspects of the formation and stabilization of the condensates, one less studied feature is the role of external perturbative fluid flow. In fact, in living cells, shear stress may arise from streaming or active transport processes. Here, we investigate how biomolecular condensates are deformed under different types of shear flows. We first model Couette flow perturbations via two-way coupling between the condensate dynamics and fluid flow by deploying Lattice Boltzmann Molecular Dynamics. We then show that a simplified approach where the shear flow acts as a static perturbation (one-way coupling) reproduces the main features of the condensate deformation and dynamics as a function of the shear rate. With this approach, which can be easily implemented in molecular dynamics simulations, we analyze the behavior of biomolecular condensates described through residue-based coarse-grained models, including intrinsically disordered proteins and protein/RNA mixtures. At lower shear rates, the fluid triggers the deformation of the condensate (spherical to oblated object), while at higher shear rates, it becomes extremely deformed (oblated or elongated object). At very high shear rates, the condensates are fragmented. We also compare how condensates of different sizes and composition respond to shear perturbation, and how their internal structure is altered by external flow. Finally, we consider the Poiseuille flow that realistically models the behavior in microfluidic devices in order to suggest potential experimental designs for investigating fluid perturbations in vitro. 

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