Molecular crowding effects on the distribution of amphiphiles in biological media

Patrícia A.T. Martins, Neuza Domingues, Cristiana Pires, Ana Maria Alves, Tiago Palmeira, Jaime Samelo, Renato Cardoso, Adrian Velazquez-Campoy, Maria João Moreno

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)


Biological systems are the result of the interactions established among their many distinct molecules and molecular assemblies. The high concentration of small molecules dissolved in the aqueous media alter the water properties with important consequences in the interactions established. In this work, the effects of high concentrations of the disaccharide trehalose on the solubility of a homologous series of fluorescent amphiphiles (NBD-Cn, n=4–16) and on their interaction with a lipid bilayer and a serum protein are quantitatively characterized. Both kinetic and equilibrium aspects are reported for a better understanding of the effects observed. The aqueous solubility of the most hydrophobic amphiphiles (n ≥ 8) is strongly increased by 1 M trehalose, while no signifcant effect is observed for the most polar amphiphile (n = 4). This results from a decrease in the magnitude of the hydrophobic effect at molecular crowding conditions. A small decrease is observed on the equilibrium association with serum albumin. This is most significant for amphiphiles with longer alkyl chains, in agreement with their increased solubility in the aqueous media containing trehalose. The effects on the association of the amphiphiles with lipid bilayers are influenced by both equilibrium and kinetic aspects. On the one hand, the decreased magnitude of the hydrophobic effect leads to a decrease in the affinity of the amphiphiles towards the membrane. However, this tendency may be overbalanced by the effects on the kinetics of the interaction (insertion/desorption) due to the increase in the viscosity of the aqueous media. It is shown that the distribution of amphiphilic drugs in the crowded biological media is significantly different from that predicted from studies in dilute solutions and that the effects are dependent on the solute's hydrophobicity.

Original languageEnglish
Pages (from-to)319-325
Number of pages7
JournalColloids and Surfaces B: Biointerfaces
Publication statusPublished - 1 Aug 2019


  • Amphiphiles
  • Equilibrium distribution
  • Kinetics
  • Molecular crowding effects
  • Pharmacokinetics
  • Solubility


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