Using membrane composition to fine-tune the pK_a of an optical liposome pH sensor

Liposomes containing membrane-anchored pH-sensitive optical probes are valuable sensors for monitoring pH in various biomedical samples. The dynamic range of the sensor is maximized when the probe pK_a is close to the expected sample pH. While some biomedical samples are close to neutral pH there are several circumstances where the pH is 1 or 2 units lower. Thus, there is a need to fine-tune the probe pK_a in a predictable way. This investigation examined two lipid-conjugated optical probes, each with appended deep-red cyanine dyes containing indoline nitrogen atoms that are protonated in acid. The presence of anionic phospholipids in the liposomes stabilized the protonated probes and increased the probe pK_a values by < 1 unit. The results show that rational modification of the membrane composition is a general non-covalent way to fine-tune the pK_a of an optical liposome sensor for optimal pH sensing performance.