fluctuations of the cell’s equator in only a limited range of modes. Lower
modes fail owing to the closed shape of a cell, whereas higher modes
fail because of optical and temporal resolution. This model considers
fluctuations as having a thermal origin. equation ( 1 ) has limiting behav-
iours, as shown in a representative fluctuation power spectrum in Sup-
plementary Information Section S2: the tension term (q−1 behaviour)
dominates at low modes, while the bending modulus term (q−3 trend)
dominates at high modes. In the range 8–20, for the parameters of
RBCs, both terms contribute to equation ( 1 ) and so both can be resolved
robustly and independently, as shown in Extended Data Figs. 5, 9. We
decided to use modes between 8 and 20 through the calculus of the
residues shown in Extended Data Fig. 10a. We quantified the viscosity
of RBCs by measuring the dynamics of the membrane fluctuations
and their relaxation time for modes 7–11 (Extended Data Fig. 10b and
Supplementary Information Section S2). This is a further independent
check confirming that the static study is measuring reliable values of
tension (Extended Data Fig. 10c).
Reporting summary
Further information on research design is available in the Nature
Research Reporting Summary linked to this paper.
Data availability
The authors declare that the data supporting the findings of this study
are available within the manuscript and its Supplementary Information
files. Source data are provided with this paper.
- Gilson, P. R. & Crabb, B. S. Morphology and kinetics of the three distinct phases of red
blood cell invasion by Plasmodium falciparum merozoites. Int. J. Parasitol. 39 , 91–96
(2009). - Yoon, Y. Z., Kotar, J., Yoon, G. & Cicuta, P. The nonlinear mechanical response of the red
blood cell. Phys. Biol. 5 , 036007 (2008). - Nightingale, K. et al. High-definition analysis of host protein stability during human
cytomegalovirus infection reveals antiviral factors and viral evasion mechanisms. Cell
Host Microbe 24 , 447–460 (2018). - McAlister, G. C. et al. MultiNotch MS3 enables accurate, sensitive, and multiplexed
detection of differential expression across cancer cell line proteomes. Anal. Chem. 86 ,
7150–7158 (2014).
34. Cox, J. & Mann, M. MaxQuant enables high peptide identification rates, individualized
p.p.b.-range mass accuracies and proteome-wide protein quantification. Nat. Biotechnol.
26 , 1367–1372 (2008).
35. Huttlin, E. L. et al. A tissue-specific atlas of mouse protein phosphorylation and
expression. Cell 143 , 1174–1189 (2010).
36. Krogh, A., Larsson, B., von Heijne, G. & Sonnhammer, E. L. Predicting transmembrane
protein topology with a hidden Markov model: application to complete genomes. J. Mol.
Biol. 305 , 567–580 (2001).
37. Pécréaux, J., Döbereiner, H. G., Prost, J., Joanny, J. F. & Bassereau, P. Refined contour
analysis of giant unilamellar vesicles. Eur. Phys. J. E 13 , 277–290 (2004).
Acknowledgements We thank E. Mabibo, J. Golijo, A. Kazungu, R. Mwarabu, the staff of Kilifi
County Hospital and the KEMRI–Wellcome Trust Research Programme, Kilifi, for their help with
participant recruitment and data and sample collection; and E. Leffler and G. Band for
discussions on the study. We also thank the study participants and their parents for agreeing to
participate in this study. J.C.R., A.M. and D.K. were supported by the Wellcome Trust (grant
206194/Z/17/Z). We acknowledge V. Lew and T. Tiffert for the provision of fresh blood and
useful discussions. M.P.W. is funded by a Wellcome Senior Fellowship (grant 108070). T.N.W. is
funded by fellowships awarded by the Wellcome Trust (grants 091758 and 202800). S.N.K. is
supported by a Wellcome Trust funded Initiative to Develop African Research Leaders (IDeAL)
early-career postdoctoral fellowship (107769/Z/10/Z), supported through the Developing
Excellence in Leadership, Training and Science (DELTAS) Africa Initiative (DEL-15-003). The
Wellcome Trust provides core support to the KEMRI/Wellcome Trust Research Programme,
Kilifi, Kenya (084535), the Wellcome Sanger Institute, Cambridge, UK (206194/Z/17/Z) and
the Wellcome Centre for Human Genetics, Oxford, UK (090532/Z/09/Z and 203141). P.C. is
supported by the Engineering and Physical Sciences Research Council (EPSRC);
EP/R011443/1), and V.I. is supported by the EPSRC and a Sackler fellowship. This paper is
published with permission from the director of KEMRI.
Author contributions S.N.K., A.M.-M., V.I., B.J.R., Y.-C.L., M.P.W., P.C., T.N.W. and J.C.R.
conceived and planned the experiments. S.N.K. and A.M.-M. carried out genotyping, RBC
preference invasion and RBC membrane protein characterization by flow cytometry. V.I. and
Y.-C.L. performed live video imaging. V.I. carried out optical-tweezer experiments and RBC
membrane contour detection and flickering spectrometry. B.J.R. performed the RBC plasma
membrane profiling. Each of the authors analysed the experiments that they had carried out.
A.M., J.M., M.T. and W.N. contributed to sample preparation and genotyping. J.K., M.C., J.A.R.,
K.R. and D.K. contributed to the interpretation of the results. All authors provided essential
feedback and helped to shape the research, analysis and manuscript.Competing interests The authors declare no competing interests.
Additional information
Supplementary information is available for this paper at https://doi.org/10.1038/s41586-020-
2726-6.
Correspondence and requests for materials should be addressed to P.C., T.N.W. or J.C.R.
Peer review information Nature thanks Brendan Crabb, Leann Tilley and the other,
anonymous, reviewer(s) for their contribution to the peer review of this work.
Reprints and permissions information is available at http://www.nature.com/reprints.