# Exploring the Limits of Passive Macromolecular Translocation through Phospholipid Membranes

## TL;DR

This paper investigates how alternating amphiphilic polymers can passively move through lipid membranes, revealing how their structure affects translocation speed and behavior.

## Contribution

The study introduces alternating amphiphilic polymers as a tunable model to explore passive translocation through lipid membranes.

## Key findings

- AAPs with small hydrophilic/hydrophobic units show homopolymer-like behavior and high membrane solubility.
- Increasing hydrophilic unit size reduces membrane solubility and translocation speed.
- AAPs with balanced hydrophilic and hydrophobic units exhibit fast translocation due to strong amphiphilic character.

## Abstract

Transportation of
active macromolecules through cell membranes
is an essential biological process. However, for hydrophilic macromolecules,
the hydrophobic interior of lipid bilayers suppresses the passive
translocation, and there are only few cases reported. We use alternating
amphiphilic polymers (AAPs) in which the sizes of the hydrophilic
and hydrophobic units can be varied over a broad range, keeping the
polymers water-soluble. For small units, the macromolecules show a
homopolymer-like character. Pulse field gradient NMR and neutron reflectivity
measurements show that the chains have a high solubility in the membrane
hydrophobic interior that allows the chains to passively translocate.
Increasing the length of the hydrophilic units leads to more polar
AAPs with low membrane solubility and a reduced translocation speed.
If hydrophilic and hydrophobic moieties are increased in size, the
AAPs have a strong amphiphilic character and adsorb to lipid membranes
only with their hydrophobic units, have a high membrane concentration,
and have an overall fast translocation kinetics.