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Surface area-to-volume ratio, not cellular viscoelasticity, is the major determinant of red blood cell traversal through small channels.

ABSTRACT: The remarkable deformability of red blood cells (RBCs) depends on the viscoelasticity of the plasma membrane and cell contents and the surface area to volume (SA:V) ratio; however, it remains unclear which of these factors is the key determinant for passage through small capillaries. We used a microfluidic device to examine the traversal of normal, stiffened, swollen, parasitised and immature RBCs. We show that dramatic stiffening of RBCs had no measurable effect on their ability to traverse small channels. By contrast, a moderate decrease in the SA:V ratio had a marked effect on the equivalent cylinder diameter that is traversable by RBCs of similar cellular viscoelasticity. We developed a finite element model that provides a coherent rationale for the experimental observations, based on the nonlinear mechanical behaviour of the RBC membrane skeleton. We conclude that the SA:V ratio should be given more prominence in studies of RBC pathologies.

SUBMITTER: Namvar A

PROVIDER: S-EPMC7757199 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Surface area-to-volume ratio, not cellular viscoelasticity, is the major determinant of red blood cell traversal through small channels.

Namvar Arman A Blanch Adam J AJ Dixon Matthew W MW Carmo Olivia M S OMS Liu Boyin B Tiash Snigdha S Looker Oliver O Andrew Dean D Chan Li-Jin LJ Tham Wai-Hong WH Lee Peter V S PVS Rajagopal Vijay V Tilley Leann L

Cellular microbiology 20201007 1

The remarkable deformability of red blood cells (RBCs) depends on the viscoelasticity of the plasma membrane and cell contents and the surface area to volume (SA:V) ratio; however, it remains unclear which of these factors is the key determinant for passage through small capillaries. We used a microfluidic device to examine the traversal of normal, stiffened, swollen, parasitised and immature RBCs. We show that dramatic stiffening of RBCs had no measurable effect on their ability to traverse sma ...[more]

PMID: 32981231

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Project description:Rationale: Airway remodeling in chronic obstructive pulmonary disease (COPD) is due to luminal narrowing and/or loss of airways. Existing computed tomographic metrics of airway disease reflect only components of these processes. With progressive airway narrowing, the ratio of the airway luminal surface area to volume (SA/V) should increase, and with predominant airway loss, SA/V should decrease.Objectives: To phenotype airway remodeling in COPD.Methods: We analyzed the airway trees of 4,325 subjects with COPD Global Initiative for Chronic Obstructive Lung Disease stages 0 to 4 and 73 nonsmokers enrolled in the multicenter COPDGene (Genetic Epidemiology of COPD) cohort. Surface area and volume measurements were estimated for the subtracheal airway tree to derive SA/V. We performed multivariable regression analyses to test associations between SA/V and lung function, 6-minute-walk distance, St. George's Respiratory Questionnaire, change in FEV1, and mortality, adjusting for demographics, total airway count, airway wall thickness, and emphysema. On the basis of the change in SA/V over 5 years, we categorized subjects into predominant airway narrowing [positive ∆(SA/V) more than 0] and predominant airway loss [negative ∆(SA/V) less than 0] and compared survival between the two groups.Measurements and Main Results: Airway SA/V was independently associated with FEV1/FVC (β = 0.12; 95% confidence interval [CI], 0.09-0.14; P < 0.001) and FEV1% predicted (β = 20.10; 95% CI, 15.13-25.08; P < 0.001). Airway SA/V was also independently associated with 6-minute-walk distance, respiratory quality of life, and lung function decline. Compared with subjects with predominant airway narrowing (n = 2,914; 66.3%), those with predominant airway loss (n = 1,484; 33.7%) had worse survival (adjusted hazard ratio for all-cause mortality = 1.58; 95% CI, 1.18-2.13; P = 0.002).Conclusions: Computed tomography-based airway SA/V is an imaging biomarker of airway remodeling and provides differential information on predominant airway narrowing and loss in COPD. SA/V is associated with respiratory morbidity, lung function decline, and survival.

Dataset Information

Surface area-to-volume ratio, not cellular viscoelasticity, is the major determinant of red blood cell traversal through small channels.

Publications

Surface area-to-volume ratio, not cellular viscoelasticity, is the major determinant of red blood cell traversal through small channels.

Similar Datasets

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