Biomechanical Dependence of SARS-CoV-2 Infections
Artikel i vetenskaplig tidskrift, 2022

Older people have been disproportionately vulnerable to the current SARS-CoV-2 pandemic, with an increased risk of severe complications and death compared to other age groups. A mix of underlying factors has been speculated to give rise to this differential infection outcome including changes in lung physiology, weakened immunity, and severe immune response. Our study focuses on the impact of biomechanical changes in lungs that occur as individuals age, that is, the stiffening of the lung parenchyma and increased matrix fiber density. We used hydrogels with an elastic modulus of 0.2 and 50 kPa and conventional tissue culture surfaces to investigate how infection rate changes with parenchymal tissue stiffness in lung epithelial cells challenged with SARS-CoV-2 Spike (S) protein pseudotyped lentiviruses. Further, we employed electrospun fiber matrices to isolate the effect of matrix density. Given the recent data highlighting the importance of alternative virulent strains, we included both the native strain identified in early 2020 and an early S protein variant (D614G) that was shown to increase the viral infectivity markedly. Our results show that cells on softer and sparser scaffolds, closer resembling younger lungs, exhibit higher infection rates by the WT and D614G variant. This suggests that natural changes in lung biomechanics do not increase the propensity for SARS-CoV-2 infection and that other factors, such as a weaker immune system, may contribute to increased disease burden in the elderly.

pseudotyped virus

extracellular matrix density

infection

aging

SARS-CoV-2

lungs

biomechanics

Författare

Alexandra Paul

Chalmers, Biologi och bioteknik, Kemisk biologi

Sachin Kumar

Indian Institute of Technology Delhi

Tamer S. Kaoud

The University of Texas at Austin

Madison R. Pickett

The University of Texas at Austin

Amanda L. Bohanon

The University of Texas at Austin

Janet Zoldan

The University of Texas at Austin

Kevin N. Dalby

The University of Texas at Austin

Sapun H. Parekh

The University of Texas at Austin

ACS Applied Bio Materials

25766422 (ISSN)

Lipidkroppars växelverkan med amyloida protein i neurodegenerativa sjukdomar: avbildande mikroskopi på cellnivå

Vetenskapsrådet (VR) (2019-00682), 2019-07-01 -- 2022-06-30.

Ämneskategorier

Infektionsmedicin

Immunologi inom det medicinska området

Mikrobiologi inom det medicinska området

DOI

10.1021/acsabm.2c00143

Mer information

Skapat

2022-05-02