Skip to main content
Log in

Investigating cell functioning by theoretical analysis of cell-to-cell variability

  • Review
  • Published:
European Biophysics Journal Aims and scope Submit manuscript

Abstract

Here we discuss cell-to-cell variability in isogenic cell populations on the basis of an analogy between the processes of vesicle self-reproduction and cell self-replication. A short review of the theoretical analysis of vesicle self-reproduction is presented to indicate that this process only occurs under the fulfillment of specific criteria: causal relations between the values of vesicle variables involved in its growth and division, and the parameters of the environment. It is shown that when division is asymmetric, both vesicle birth size and interdivision times are variable. We argue that during cell self-replication, the balance between processes of cell growth and division also relies on causal relations between the corresponding cellular variables. A possible method is suggested to unravel previously unidentified causal relations between cell variables from the relationships between their variability parameters such as the widths of their probability distributions and their correlation coefficients. The method is outlined by reviewing the results of the corresponding analysis applied to a population of red blood cells. Some novel research directions are suggested that could lead from the analysis of cell-to-cell variability to a better understanding of the organizational structure of cells and possibly also their evolutionary origin.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

(Adapted from Božič and Svetina 2007)

Similar content being viewed by others

References

  • Berclaz N, Müller M, Walde P, Luisi PL (2001) Growth and transformation of vesicles studied by ferritin labeling and cryotransmission electron microscopy. J Phys Chem B 105:1056–1064

    Article  CAS  Google Scholar 

  • Bessman JD, Ridgway Gilmer Jr P, Gardner FH (1983) Improved classification of anemias by MCV and RDW. Am J Clin Path 80:322–326

    Article  CAS  PubMed  Google Scholar 

  • Božič B, Svetina S (2004) A relationship between membrane properties forms the basis of a selectivity mechanism for vesicle self-reproduction. Eur Biophys J 33:565–571

    Article  PubMed  Google Scholar 

  • Božič B, Svetina S (2007) Vesicle self-reproduction: the involvement of membrane hydraulic and solute permeabilities. Eur Phys J E 24:79–90

    Article  PubMed  Google Scholar 

  • Brumen M, Glaser R, Svetina S (1979) Osmotic states of the red blood cell. Bioelectrochem Bioenerg 6:227–241

    Article  CAS  Google Scholar 

  • Canham PB, Burton AC (1968) Distribution of size and shape in populations of normal human red cells. Circ Res 22:405–422

    Article  CAS  PubMed  Google Scholar 

  • Cerulus B, New AM, Pougach K, Verstrepen KJ (2016) Noise and epigenetic inheritance of single-cell division times influence population fitness. Curr Biol 26:1138–1147

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cossins AR, Gibson JS (1997) Volume-sensitive transport systems and volume homeostasis in vertebrate red blood cells. J Exp Biol 200:343–352

    CAS  PubMed  Google Scholar 

  • Dawson KB, Madoc-Jones H, Field EO (1965) Variations in the generation times of a strain of rat sarcoma cells in culture. Exp Cell Res 38:75–84

    Article  CAS  PubMed  Google Scholar 

  • Dervaux J, Noireaux V, Libchaber AJ (2017) Growth and instability of a phospholipid vesicle in a bath of fatty acids. Eur Phys J Plus 132:284

    Article  Google Scholar 

  • Deuling HJ, Helfrich W (1976) The curvature elasticity of fluid membranes: a catalogue of vesicle shapes. J Phys Fr 37:1334–1345

    Google Scholar 

  • Franco RS, Puchulu-Campanella ME, Barber LA, Palascak MB, Joiner CH, Low PS, Cohen RM (2013) Changes in properties of normal human red blood cells during in vivo aging. Am J Hematol 88:44–51

    Article  CAS  PubMed  Google Scholar 

  • Freedman JC, Hoffman JF (1979) Ionic and osmotic equilibria of human red blood cells treated with nystatin. J Gen Physiol 74:187–212

    Article  CAS  PubMed  Google Scholar 

  • Furusawa C, Suzuki T, Kashiwagi A, Yomo T, Kaneko K (2005) Ubiquity of log-normal distributions in intracellular reactions dynamics. Biophysics 1:25–31

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huh D, Paulsson J (2011) Non-genetic heterogeneity from asymmetric cell partitioning. Nat Genet 43:95–100

    Article  CAS  PubMed  Google Scholar 

  • Jimbo T, Sakuma Y, Urakami N, Ziherl P, Imai M (2016) Role of inverse-cone-shape lipids in temperature-controlled self-reproduction of binary vesicles. Biophys J 110:1551–1562

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Korn GA, Korn TM (1968) Mathematical handbook for scientists and engineers. Chap 18. McGraw-Hill, New York

    Google Scholar 

  • Lew VL, Bookchin RM (1986) Volume, pH and ion content regulation in human red cells: analysis of transient behavior with an integrated model. J Membr Biol 92:57–74

    Article  CAS  PubMed  Google Scholar 

  • Lew VL, Raftos JE, Sorette M, Bookchin RM, Mohandas N (1995) Generation of normal human red cell volume, hemoglobin content, and membrane area distributions by “birth” or regulation? Blood 86:334–341

    CAS  PubMed  Google Scholar 

  • Mizrahi SP, Sandler O, Lande-Diner L, Balaban NQ, Simon I (2015) Distinguishing between stochasticity and determinism: example from cell cycle duration variability. BioEssays 38:8–13

    Article  Google Scholar 

  • Mohandas N, Kim YR, Tycko DH, Orlik J, Wyatt J, Groner W (1986) Accurate and independent measurement of volume and hemoglobin concentration of individual red cells by laser light scattering. Blood 68:506–513

    CAS  PubMed  Google Scholar 

  • Newman JRS, Ghaemmaghani S, Ihmels J, Breslow DK, Noble M, DeRisi J, Weissman JS (2006) Single-cell proteomic analysis of S. cerevisiae reveals the architecture of biological noise. Nature 441:840–846

    Article  CAS  PubMed  Google Scholar 

  • Nishimura K, Tsuru S, Suzuki H, Yomo T (2015) Stochasticity in gene expression in a cell-sized compartment. ACS Synth Biol 4:566–576

    Article  CAS  PubMed  Google Scholar 

  • Peterlin P, Arrigler V, Kogej K, Svetina S, Walde P (2009) Growth and shape transformations of giant phospholipid vesicles upon interaction with an aqueous oleic acid suspension. Chem Phys Lipids 159:67–76

    Article  CAS  PubMed  Google Scholar 

  • Sandler O, Mizrahi SP, Weiss N, Agam O, Simon I, Balaban NQ (2015) Lineage correlations of single cell division time as a probe of cell-cycle dynamics. Nature 519:468–471

    Article  CAS  PubMed  Google Scholar 

  • Sauls JT, Li D, Jun S (2016) Adder and a coarse-grained approach to cell size homeostasis in bacteria. Curr Opin Cell Biol 38:38–44

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schonbrun E, Malka R, Di Caprio G, Schaak D, Higgins JM (2014) Quantitative absorption cytometry for measuring red blood cell hemoglobin mass and volume. Cytometry 85A:332–338

    Article  CAS  Google Scholar 

  • Seifert U, Berndl K, Lipowsky R (1991) Shape transformations of vesicles: phase diagram for spontaneous curvature and bilayer coupling models. Phys Rev A 44:1182–1202

    Article  CAS  PubMed  Google Scholar 

  • Sigal A, Milo R, Cohen A, Geva-Zatorsky N, Klein Y, Liron Y, Rosenfeld N, Danon T, Perzov N, Alon R (2006) Variability and memory of protein levels in human cells. Nature 444:643–646

    Article  CAS  PubMed  Google Scholar 

  • Snijder B, Sacher R, Pauli R, Damm E-M, Liberali P, Pelkmans L (2009) Population context determines cell-to-cell variability in endocytosis and virus infection. Nature 461:520–523

    Article  CAS  PubMed  Google Scholar 

  • Spudich JL, Koshland DE (1976) Non-genetic individuality—chance in single cells. Nature 262:467–471

    Article  CAS  PubMed  Google Scholar 

  • Stano P, Wehrli E, Luisi PL (2006) Insights into the self-reproduction of oleate vesicles. J Phys Condens Matter 18:2231–2238

    Article  Google Scholar 

  • Svetina S (1981) On cell population variations of red blood cell membrane properties. In: Kuczera J, Grygorczyk C, Przestalski S (eds) Sixth school on biophysics of membrane transport. Agricultural University of Wrocław, Wrocław, pp 296–310

    Google Scholar 

  • Svetina S (1982) Relations among variations in human red cell volume, density, membrane area, hemoglobin content and cation content. J Theor Biol 95:123–134

    Article  CAS  PubMed  Google Scholar 

  • Svetina S (2007) The vesicle world: the emergence of cellular life can be related to properties specific to vesicles. Orig Life Evol Biosph 39:445–448

    Article  Google Scholar 

  • Svetina S (2012a) Cellular life could have emerged from properties of vesicles. Orig Life Evol Biosph 42:483–486

    Article  PubMed  Google Scholar 

  • Svetina S (2012b) On the vesicular origin of the cell cycle. In: Seckbach J (ed) Genesis—in the beginning: precursors of life, chemical models and early biological evolution. Springer Science + Business Media, Dordrecht, pp 757–773

    Chapter  Google Scholar 

  • Svetina S, Žekš B (1989) Membrane bending energy and shape determination of phospholipid vesicles and red blood cells. Eur Biophys J 17:101–111

    Article  CAS  PubMed  Google Scholar 

  • Svetina S, Brumen M, Gros M, Vrhovec S, Žnidarčič T (2003) On the variation of parameters that characterize the state of a physiological system. Red blood cells as an example. In: Arnež ZM, Brebbia CA, Solina F, Stankovski V (eds) Simulations in biomedicine V. WITT Press, Southampton, pp 3–14

    Chapter  Google Scholar 

Download references

Acknowledgements

The work was partly supported by the Slovenian Research Agency (Grant P1-0055).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Saša Svetina.

Additional information

Special Issue: Regional Biophysics Conference 2016.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Svetina, S. Investigating cell functioning by theoretical analysis of cell-to-cell variability. Eur Biophys J 46, 739–748 (2017). https://doi.org/10.1007/s00249-017-1258-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00249-017-1258-y

Keywords

Navigation