How do manufactured nanoparticles enter cells?

A problem presented at the UK MMSG Reading 2011.

Presented by:
Prof Kevin Chipman (Biosciences, University of Birmingham)
Prof Jon Preece (Chemistry, University of Birmingham)
Dr Joshua Rappoport (School of Biosciences, University of Birmingham)
II Argatov, JK Chipman, ABM Davies, L Dyson, RJ Dyson, AEW Johnson, GE Lang, M Mayaud, S Payvandi, JM Phillips, CP Please, FM Pool, AC Pratt, A Preece, JZ Rappoport, A Roebuck, T Saratoon, TP Warzocha

Problem Description

The ever increasing production and use of manufactured nanoparticles in industry, research and medicine, has led to greater potential for incidental environmental exposure, as well as deliberate contact through products and therapeutics. However, the potential for cellular entry and toxicity of manufactured nanoparticles has only recently begun to be investigated.

The cell is bound by the plasma membrane, a lipid bilayer which contains opposing monolayers, or leaflets, of phospholipids with the hydrophilic head groups facing the extracellular and intracellular solutions, and the hydrophobic tails facing each other. Generally speaking three routes for nanoparticle entry into cells exist, each of which must be analysed independently before a comprehensive model can be formed. These are: (i) direct diffusion; (ii) endocytosis; and (iii) ion channels and transporter proteins.

The Study Group participants are asked to help with answering the following questions:

  1. What are the relevant parameters that need to be considered regarding nanoparticle composition and the nano-bio interface?
  2. Can a model for diffusion of nanoparticles across the plasma membrane be generated that is robust enough to account for all potential variables?
  3. Can a model of nanoparticle endocytosis be generated that includes all potential trafficking pathways?
  4. Can nanoparticle entry through plasma membrane channels and transporters truly be excluded?
  5. Can an integrated model describing all potential means of nanoparticle entry into cells be produced?

Download the full problem description

Study Group Report

Our aim during the study group week was to analyse the differing mechanisms of nanoparticle entry into cells, and if possible to explain the role of serum in decreasing nanoparticle association with cells. A variety of different initial models were developed.

Download the full report

Follow-Up Activities

The following publications have been written as a result of this problem:

Cellular entry of nanoparticles via serum sensitive clathrin-mediated endocytosis, and plasma membrane permeabilization
PJ Smith, M Giroud, HL Wiggins, F Gower, JA Thorley, B Stolpe, J Mazzolini, RJ Dyson, JZ Rappoport (2012)
International Journal of Nanomedicine 2012 (7), 2045–2055.

The following follow-up meetings have occured to continue work on aspects of this problem:

2012 Nanoparticles Follow-up Meeing
Monday 30th January 2012, University of Birmingham