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Tethered cells in fluid flows: beyond the Stokes’ drag force approach
Umeå University, Faculty of Science and Technology, Department of Physics. Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
Umeå University, Faculty of Science and Technology, Department of Physics. Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
Umeå University, Faculty of Science and Technology, Department of Physics. Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
Umeå University, Faculty of Science and Technology, Department of Physics. Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
2015 (English)In: Physical Biology, ISSN 1478-3967, E-ISSN 1478-3975, Vol. 12, 056006Article in journal (Refereed) Published
Abstract [en]

Simulations of tethered cells in viscous sub-layers are frequently performed using the Stokes' drag force, but without taking into account contributions from surface corrections, lift forces, buoyancy, the Basset force, the cells' finite inertia, or added mass. In this work, we investigate to what extent such contributions, under a variety of hydrodynamic conditions, influence the force at the anchor point of a tethered cell and the survival probability of a bacterium that is attached to a host by either a slip or a catch bond via a tether with a few different biomechanical properties. We show that a consequence of not including some of these contributions is that the force to which a bond is exposed can be significantly underestimated; in general by similar to 32-46%, where the influence of the surface corrections dominate ( the parallel and normal correction coefficients contribute similar to 5-8 or similar to 23-26%, respectively). The Basset force is a major contributor, up to 20%, for larger cells and shear rates. The lift force and inertia contribute when cells with radii >3 mu m have shear rates>2000 s(-1). Buoyancy contributes significantly for cells with radii > 3 mu m for shear rates<10 s(-1). Since the lifetime of a bond depends strongly on the force, both the level of approximation and the biomechanical model of the tether significantly affect the survival probability of tethered bacteria. For a cell attached by a FimH-mannose bond and an extendable tether with a shear rate of 3000 s(-1), neglecting the surface correction coefficients or the Basset force can imply that the survival probability is overestimated by more than an order of magnitude. This work thus shows that in order to quantitatively assess bacterial attachment forces and survival probabilities, both the fluid forces and the tether properties need to be modeled accurately.

Place, publisher, year, edition, pages
2015. Vol. 12, 056006
National Category
Other Physics Topics
Identifiers
URN: urn:nbn:se:umu:diva-106875DOI: 10.1088/1478-3975/12/5/056006ISI: 000362005900010PubMedID: 26331992OAI: oai:DiVA.org:umu-106875DiVA: diva2:845420
Funder
Swedish Research Council, 2013-5379Swedish Research Council, 621-2008-3280
Available from: 2015-08-11 Created: 2015-08-11 Last updated: 2017-12-04Bibliographically approved
In thesis
1. The mechanics of adhesion polymers and their role in bacterial attachment
Open this publication in new window or tab >>The mechanics of adhesion polymers and their role in bacterial attachment
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Bacterial resistance to antibiotics is increasing at a high rate in both developing and developed countries. To circumvent the problem of drug-resistant bacterial pathogens, we need to develop new effective methods, substances, and materials that can disarm and prevent them from causing infections. However, to do this we first need to find new possible targets in bacteria to approach and novel strategies to apply.Escherichia coli (E. coli) bacteria is a normal member of the intestinal microflora of humans and mammals, but frequently cause diverse intestinal and external diseases by means of virulence factors, which leads to hundreds of million sick people each year with a high mortality rate. An E. coli bacterial infection starts with adhesion to a host cell using cell surface expressed adhesion polymers, called adhesion pili. Depending on the local environment different types of pili are expressed by the bacteria. For example, bacteria found in the gastrointestinal tract commonly express different pili in comparison to those found in the urinary tract and respiratory tract. These pili, which are vital for bacterial adhesion, thereby serve as a new possible approach in the fight against bacterial infections by targeting and disabling these structures using novel chemicals. However, in order to develop such chemicals, better understanding of these pili is needed.Optical tweezers (OT) can measure and apply forces up to a few hundred pN with sub-pN force resolution and have shown to be an excellent tool for investigating mechanical properties of adhesion pili. It has been found that pili expressed by E. coli have a unique and complex force-extension response that is assumed to be important for the ability of bacteria to initiate and maintain attachment to the host cells. However, their mechanical functions and the advantage of specific mechanical functions, especially in the initial attachment process, have not yet been fully understood.In this work, a detailed description of the pili mechanics and their role during cell adhesion is presented. By using results from optical tweezers force spectroscopy experiments in combination with physical modeling and numerical simulations, we investigated how pili can act as “shock absorbers” through uncoiling and thereby lower the fluid force acting on a bacterium. Our result demonstrate that the dynamic uncoiling capability of the helical part of the adhesion pili modulate the force to fit the optimal lifetime of its adhesin (the protein that binds to the receptor on the host cell), ensuring a high survival probability of the bond.iiiSince the attachment process is in proximity of a surface we also investigated the influence of tether properties and the importance of different surface corrections and additional force components to the Stokes drag force during simulations. The investigation showed that the surface corrections to the Stokes drag force and the Basset force cannot be neglected when simulating survival probability of a bond, since that can overestimate the probability by more than an order of magnitude.Finally, a theoretical and experimental framework for two separate methods was developed. The first method can detect the presence of pili on single cells using optical tweezers. We verified the method using silica microspheres coated with a polymer brush and E. coli bacteria expressing; no pili, P pili, and type 1 pili, respectively. The second method was based on digital holography microscopy. Using the diffraction of semi-transparent object such as red blood cells, we showed that this method can reconstruct the axial position and detect morphological changes of cells.

Place, publisher, year, edition, pages
Umeå: Umeå universitet, 2015. 65 p.
Keyword
Pili, optical tweezers, bacterial adhesion, fimbriae, uncoiling
National Category
Other Physics Topics Biophysics
Identifiers
urn:nbn:se:umu:diva-109524 (URN)978-91-7601-331-1 (ISBN)
Public defence
2015-10-23, Naturvetarhuset, N420, Umeå universitet, Umeå, 13:00 (English)
Opponent
Supervisors
Available from: 2015-10-02 Created: 2015-09-30 Last updated: 2015-10-02Bibliographically approved

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Zakrisson, JohanWiklund, KristerAxner, OveAndersson, Magnus

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